Intern.李家騏 Supervisor: Dr. 沈靜芬 2019/5/10 Clinical case presentation: one female newborn presented with fever and tachypnea after birth Intern.李家騏 Supervisor: Dr. 沈靜芬

Identifying information 2019/5/10 Identifying information Name: 方X涵 Chart number: 170xx746 Sex: female Age: Newborn Date of birth and admission: 7/19

On admission Fever after birth (rectal temperature: 38.3’ C) 2019/5/10 On admission She was presented with Fever after birth (rectal temperature: 38.3’ C) Tachypnea, nasal flaring and subcostal retraction SpO2:97% Normal PO2 in newborn: 40-70 mmHg Na:133-146 K:4.6-6.7 C:8.1-11 P:6.2-8.7 Cl:102-116

On admission Birth history: 2019/5/10 On admission Birth history: GA: 35+6 weeks, late preterm G5P1AA4, Cesarean section due to maternal fever, DOIC(-), PPROM (-) (7/19 9:38 ROM; 9:39 birth) Apar score: 6 ---> 9 Birth body weight:2195g (borderline SGA; 10th %); Body length: 44cm (10-25th %); Head circumstances: 33cm (75-90th %) His prenatal care at our OPD was uneventful: level II sonography revealed no fetal anomaly; no maternal GDM or PIH/pre-eclampsia; Amniocentesis(-)

2019/5/10 Maternal history (1) She went to ER due to fever up to 38.9’ C with sorethroat and general soreness on 7/18. 24-year-old female with HIV on HAART GBS(-) Lab data: Urine: WBC: 17 Influenza virus type A antigen : positive Impression: HIV infection + UTI + Influenza A  cytomegalovirus, herpes simplex virus, hepatitis B, hepatitis C, syphilis, toxoplasmosis, or tuberculosis.

2019/5/10 Maternal history Diagnosed with HIV infection since 2012, HAART at our OPD since late Janurary, 2015 (GA: 11weeks) Therapy Combivir+Azatanavir use until C/S Zidovudine 1 vial before C/S Rocephin for UTI Refused Tamiflu Lab data: HIV viral load (viral nucleic acid detection): 157 on 2/16; not detected on 5/8 and 7/22; CD4: 253.6 on 7/15  moderate suppresion Previous kaletra with severe diarrhea Antenatal steroid wasn’t used Lamivudine. +. Zidovudine

2019/5/10 Maternal history Lab data: VDRL: non-reactive on 5/6

2019/5/10 Family history Mother: HIV infection

Physical examination Physical examination revealed: 2019/5/10 Physical examination Physical examination revealed: T: 38.3’C ; P:158/min ; R:68/min BP: 62/38mmHg SpO2:97% (under nasal CPAP FiO2 26%) Abdomen: Inspection: globular Palpation: soft, no organomegaly, Percussion: tympanic Auscultation: BS: normoactive Limbs: warm, no edema, cyanosis (-), lateral weakness (-), palmar erythema (-) Peripheral pulse: symmetric and active Skin: no edema,petechiae or ecchymosis Consciousness: clear Sclera: not icteric Neck: supple, LAP (-) Chest: Inspection: symmetric expansion Palpation: no crepitus Percussion: resonance Auscultation: coarse BS Heart: Palpation: no heave, no thrill Percussion: no increase of dullness Auscultation: RHB, no murmur

Lab data 2019/5/10 Preterm Hb:15.7+-2.32 McV108.7+-6.15 Wbc: 13.9+-5.7 Plt: 245+-71.7 UTI typically presents in the second or third week after birth in term infants [1]. The incidence of UTI is low in the first few days of life (2 percent) even in neonates who are bacteremic [4]. As a result, urine cultures are not obtained for term infants who are being evaluated for early-onset sepsis before the first six days of life. 

Lab data Influenza A,B (-) Virus isolation(-) Blood culture(-) 2019/5/10 Lab data Influenza A,B (-) Virus isolation(-) Blood culture(-) CSF culture (-) 7/19 pH 7.255 PCO2 68.3 PaO2 54 HCO3 23.4 BE(ecf) -3.7 BE(B) -4.4 SaO2 89.5 7/19 Na+ 133.5 K+ 3.98 Ca2+ 1.175 Cl- 106.3 Hct(%) 40.5 Preterm Hb:15.7+-2.32 McV108.7+-6.15 Wbc: 13.9+-5.7 Plt: 245+-71.7 UTI typically presents in the second or third week after birth in term infants [1]. The incidence of UTI is low in the first few days of life (2 percent) even in neonates who are bacteremic [4]. As a result, urine cultures are not obtained for term infants who are being evaluated for early-onset sepsis before the first six days of life. 

Image 7/19 2019/5/10 Film of chest AP view shows:   1. OG tube inserted in place. 2. Coarsening of bilateral bronchivascular bundle with fine granulation of lung parenchyma, compatible with the clinical information of preterm related hyaline membrane disease. 3. Suspicious for pnemomediastinum, interval improving. 4. Both CP angles are sharp.

Impression and plan Prematurity 35+6 weeks, borderline SGA 2019/5/10 Impression and plan Impression Prematurity 35+6 weeks, borderline SGA Neonatal fever Respiratory distress Maternal HIV infection Respiratory distress, suspect TTNB or pneumonitis

Impression and plan Septic work up 2019/5/10 Impression and plan Plan in NICU Septic work up Empiric antibiotic: ampicillin + gentamicin Prophylactic anti-flu drug: Tamiflu Ventilator support (Nasal CPAP) Prophylactic antiretroviral drug : Zidovudine (six weeks) Isolation from mother breast milk 必須cover GBS, E.coli, meningitis:s.pneumonia; H.influenza, Neisseria.meningitis, listeria Ampicillin: GPC+listeria Gentamicin: GNB, pseudomona Amp+cefataxime也是選擇 因為E.coli 對gentamicin的抗藥性越來越強，而且cefataxime對BBB的穿透力強

NICU day 2 (7/20) Tachypnea and subcostal retraction 2019/5/10 NICU day 2 (7/20) Respiratory distress syndrome, Gr. II Tachypnea and subcostal retraction T/P/R:36.7/145/62 BP90/42mmHg  fever subsided Chest X ray: airbronchogram; R’t pneumomediastinum Nasal CPAP ---- Bubble CPAP NG feeding 7/20 pH 7.249 PCO2 62.3 PaO2 36.3 HCO3 26.6 BE(ecf) -0.6 BE(B) -2 SaO2 58.1

NICU day 3 (7/21) 7/21 Tachypnea (up to 100/min) 2019/5/10 Respiratory distress syndrome, Gr. II NICU day 3 (7/21) 7/21 Tachypnea (up to 100/min) Mildly improved Chest X-ray Improved gas data Start trophic feeding, SSC20 Keep Bubble CPAP 7/21 pH 7.352 PCO2 48.8 PaO2 51.8 HCO3 26.4 BE(ecf) 0.9 BE(B) 0.2 SO2 84.4

NICU day 4-8 (7/22-7/27) Improved gas data on 7/22 2019/5/10 NICU day 4-8 (7/22-7/27) Improved gas data on 7/22 Try room air on 7/26 Transfer to level II on 7/27 7/22 pH 7.353 PCO2 48.4 PaO2 60.9 HCO3 26.3 BE(ecf) 0.6 BE(B) 0.1 SaO2 89

Level II No tachypnea or subcostal retraction was noted 2019/5/10 Level II No tachypnea or subcostal retraction was noted NG feeding with SSC 20 or Donated milk as tolerance PCR I of HIV : (-) Under zidovudine (week 2)

Case discussion How to prevent perinatal HIV transmission? 2019/5/10 Case discussion How to prevent perinatal HIV transmission? How to diagnose HIV infection in newborn? Vaccination in suspected HIV-infected newborn.

How to prevent perinatal HIV transmission? Without ARV drugs during pregnancy, risk of transmission from mother to infant is 1 in 4 Pediatric AIDS Clinical Trials Group (PACTG) 076 found that by giving zidovudine (ZDV) to the pregnant woman during pregnancy, labor, and delivery, and to her newborn, transmission could be reduced to 8% The risk of perinatal transmission can now be less than 2% (1 in 50) with: Highly effective ARV therapy (HAART) Elective Cesarean section as appropriate Formula feeding  efavirenz should be avoided during the first eight weeks of pregnancy because of concern for a potential risk of neural tube defects. In contrast, treatment-experienced women with a suppressed viral load on an efavirenz-containing regimen who become pregnant should continue efavirenz.  預防母子垂直傳染的愛滋病最有效的方法，是母親懷孕第二期起服用抗<I2>病毒藥物，生產過程中施打zidovudine(ZDV)、或口服ZDV+lamivudine、或nevirapine，<I2>及嬰兒產出後不餵食母乳、並給予ZDV口服液。完善的照護可讓嬰兒得到HIV感染的機會降到百分之二以下。

How to prevent perinatal HIV transmission? In general, the risk of perinatal transmission declines with low levels of maternal HIV RNA level Women with a non-detectable viral load can still transmit HIV to their infants 若媽媽感染HIV，在整個懷孕到分娩的過程中沒有服用抗愛滋病毒藥物，則生下的嬰兒有15-30%的機率感染HIV，其中三分之一(5-10%)是在懷孕期得到的，三分之二(10-20%)則是經由產痛以及分娩過程感染；若產後又餵哺母乳至嬰兒六個月大時，則感染率會增加至25-35%；若持續餵哺母乳至兩歲，則有高達30-45%的嬰兒會感染HIV all HIV-infected pregnant women should take antiretroviral prophylaxis to prevent mother-to-child transmission of HIV, regardless of their CD4 cell counts or HIV RNA levels

How to prevent perinatal HIV transmission? During pregnancy If HIV-infected mothers took antiretroviral prophylaxis only for prevention of mother-to-child transmission Start the treatment at GA 12 week, no later than 14 weeks First choice for prevention of mother-to-child transmission was Combivir (Lamivudine, Zidovudine) Good placental permeability NRTI（nucleoside reverse-transcriptase inhibitors； Combivir (Lamivudine, Zidovudine

How to prevent perinatal HIV transmission? During labor Infants of women who have received antepartum ARV drugs but have detectable viremia (HIV RNA >1000 copies/mL) -> scheduled cesarean.  Initially Zidovudine（2 mg/kg* BW）intravenous drip for one hour, and then 1 mg/kg*BW per hour as maintain dose ZDV crosses the placenta rapidly and can provide pre-exposure prophylaxis to the fetus.

Infant antiretroviral prophylaxis How to prevent perinatal HIV transmission? Infant antiretroviral prophylaxis Maternal antepartum ARV drugs Zidovudine (ZDV) for 6 weeks, and ideally initiated within 6 - 12 hours of delivery. No maternal antepartum ARV drugs  Zidovudine prophylaxis combined with 3 doses of nevirapine in the first week of life (at birth, 48 hours later, and 96 hours after the second dose).

2. How to diagnose HIV infection in newborn? Serial qualitative DNA PCR is currently the accepted standard for early diagnosis DNA-PCR [2 consecutive readings] 1-2 months 3-6 months Antibodies (Elisa) 12 months in non-breastfed infant Others – RNA PCR, p24, viral culture Passive transfer of maternal Ig G leads to detectable antibody in uninfected children for up to 18 months Antibody tests e.g.ELISA not diagnostic until 18 months unless negative

3. Vaccination in suspected HIV-infected newborn. 疑似愛滋寶寶的疫苗接種 尚未確診感染HIV之前，其接種時程與疫苗種類與一般嬰兒無異。 確定感染HIV的嬰兒，只要沒有症狀、免疫力未低下，皆應該接種所有的不活化疫苗、麻疹、德國麻疹、腮腺炎疫苗、水痘疫苗及卡介苗。

2019/5/10 Reference

Thank you for your attention! 2019/5/10 Thank you for your attention!