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How safe is Tylenol during pregnancy?

Terri O’Connor, MSN, NNP-BC Sydney Sutton, BSN, NNC

University of Oklahoma Health Sciences Center

Disclosures �  We have nothing to disclose.

Case study �  Estimated 38+6 week by US on admission, female infant born by SVD

due to labor

�  32yo G6P5005 African American mother �  Maternal labs: O+/- Rubella immune, HBsAg/HIV/RPR/GC/CT negative,

GBS negative �  Maternal meds: Tylenol �  Pregnancy history: no prenatal care �  Medical and surgical history: depression, sickle cell trait �  Social: UDS positive for Cocaine

�  Delivery room course �  Apgars: 8 and 8 �  Resuscitation: vigorous and crying, though blue. Required blow-by, then

CPAP up to 100% for saturations. Murmur noted.

Admission assessment �  General: 3760g term female – AGA (86%ile), skin dry and peeling with meconium staining.

Dusky.

�  HEENT: AFSF, overriding sutures

�  Resp: Grunting, subcostal and intercostal retractions. Symmetrical chest rise, diminished crackles bilaterally.

�  CV: NSR, grade III-IV murmur. Pulses strong & equal, Capillary refill ~3-4 seconds.

�  Neuro: awake, appropriate tone with primitive reflexes intact. Deep sacral dimple, base visualized. Deep sacral dimple, base visualized.

�  GI/FEN: Abdomen soft and round, non-tender, bowel sounds present.

�  GU: Normal female genitalia, patent anus in normal position.

�  Heme/ID: no prenatal care, labs negative, afebrile mom, ROM at delivery with MSAF. EOS: clinical illness (treat).

Initial plan of care �  Resp: continue NIV, escalate support as indicated

�  CV: Obtain ECHO; monitor hemodynamic status and support as indicated

�  Neuro: Spinal US; minimum stimulation, consider sedation

�  GI/FEN: NPO with SNAP 10 80ml/kg/day

�  GU: monitor urine output and renal labs

�  Heme/ID: blood culture, CBC, and CRP, 48hr rule out of antibiotics.

�  Social: social services referral

�  Consults: Cardiology

Test results �  CBC: reassuring

�  CRP: reassuring

�  Blood culture: negative.

�  T&S and DAT: O+/-

�  Electrolytes: no abnormalities

�  X-rays: MAS

�  Echo: suprasystemic right ventricular pressures, no PDA, severe right ventricular hypertrophy. Severe pulmonary hypertension.

�  Umbilical cord drug screen: positive for Cocaine.

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Clinical course �  Resp: Curosurf x1; NIVàCMVàHFOV, 100% FiO2,

extubated on DOL 13, and weaned to RA by DOL 25

�  CV: required iNO and Sildenafil. Hypotensive requiring Dopamine, Dobutamine, Milrinone, and Hydrocortisone.

�  Neuro: Fentanyl, changed to Morphine, Versed and Precedex.

�  ID: 7 days of antibiotics

Diagnosis: Pulmonary Hypertension

�  Pathophysiology: �  Elevated pulmonary pressures with right-to-left shunting of deoxygenated blood from the pulmonary

to systemic circulation (Lakshminrushimha, Konduri, & Steinhorn, 2016)

�  Risk factors: �  Hypoxemic respiratory failure (Lakshminrusimha & Saugstad, 2016)

�  Perinatal asphyxia d/t abruption, cord accident, uterine rupture, etc. �  Severe oligohydramnios &/or pulmonary hypoplasia

�  Possibly due to PPROM �  Congenital diaphragmatic hernia

�  Sepsis �  Cesarean delivery without labor (Lakshminrusimha & Saugstad, 2016) �  Maternal obesity &/or diabetes (Delaney & Cornfield, 2012) �  Maternal medications: (Delaney & Cornfield, 2012)

�  SSRIs �  Ibuprofen and acetaminophen which are used to postnatally close a PDA

�  Commonly taken for back pain, hemorrhoids, uterine pain, headache or migraine, and thrombosis (Lopes et al, 2016)

Potential severe consequences of PPHN/PHTN

�  Asphyxia, including organ damage such as heart failure

�  Chronic lung disease

�  Neurodevelopmental sequelae

�  Death

Pederson et al, 2018

Transition:

Fetal vs. Neonatal circulation

Normal circulation & PPHN

University of Kansas (1996)

PPHN/PHTN

Klein (n.d)

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Management of PPHN/PHTN: initial interventions

�  Minimum stimulation

�  Maintain euglycemia, normothermia (unless therapeutic hypothermia is indicated), normal electrolytes, adequate hemoglobin and intravascular volume (Pederson et al, 2018)

�  Target higher saturations �  Oxygen therapy

�  Pre/post sat monitoring, if PDA �  Monitor shunting via ductus

�  Fluid restriction �  Must balance between need for adequate circulation and risk of

pulmonary over-circulation

Medical management �  BP management

�  Target higher MAP above TR gradient

�  Ventilation �  CMV �  HFOV- oscillators are notoriously an oxygenator d/t ability to

generate high MAP

�  Sedation �  Morphine or Fentanyl �  Versed- anxiolytic adjuvant �  Vecuronium or Rocuronium if paralysis is needed

Pharmacologic management �  Surfactant (Lakshminrusimha, Konduri, & Steinhorn, 2016)

�  Effective in reducing immediate need for respiratory support and improving clinical outcomes, especially when PHTN is secondary to pulmonary disease

�  iNO �  Powerful, selective pulmonary vasodilator that regulates pulmonary vascular tone

(Lakshminrusimha & Saugstad, 2016) �  Hypoxia reduces NO production in the pulmonary arterial endothelial cells (Aschner et al.,

2016)

�  Sildenafil (Pederson et al, 2018) �  Promotes relaxation of smooth muscle without showing adverse systemic effects

�  Prostaglandin E (Lakshminrusimha, Matthew, Leach, 2016) �  Used to promote PDA in ductal-dependent CHD �  A trial of PGE1 may be used to re-open an in-utero ductal closure to promote pulmonary

vasodilation and provide a pop-off to decrease volume & pressure overloaded right ventricle

Pharmacologic management continued

�  Inotropes such as Dopamine increase systemic blood pressure and reduce right-to-left shunting.

�  Milrinone improves left ventricular function and reduces pulmonary venous hypertension and can act synergistically with iNO.

�  Glucocorticoids �  Shown to potent anti-inflammatory properties and reduce the

duration of oxygen dependence with MAS. �  CAUTION WITH INFECTION!

(Lakshminrusimha, Konduri, & Steinhorn, 2016)

Refractory PPHN/PHTN �  ECMO

�  A type of bypass with blood oxygenated outside the body (Pederson et al, 2018)

�  Shown to reduce mortality without increasing risk for severe disability (Cochrane review, Mugford et al.)

�  Generally indicated for OI >40 without evidence of brain bleeding or other major anomalies

Is Tylenol a risk factor? �  Mom verbally reported Tylenol use and recent research has

shown a link to in-utero ductal closure (like our baby had) due to persistent and high doses of Tylenol shortly before delivery (Becquet et al., 2018).

�  We use ibuprofen and acetaminophen to treat PDAs in babies postnatally so it makes since that they would affect the ductus prenatally too since they cross the placenta.

�  DISCLAIMER: while Tylenol may possibly be responsible for in-utero ductal closure, it is generally considered safe when used as directed by obstetrics providers!

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Back to our case �  Discharge

�  Resp: RA �  CV: Echo- moderate right ventricular hypertrophy with persistent PHTN

�  Discharged home on PO Sildenafil �  Cardiology in 2 months

�  Neuro: no apparent concerns �  Developmental follow-up due to clinical course and intrauterine drug exposure

�  FEN/GI: full ad lib feeds and gaining weight �  GU: no concerns �  Heme/ID: initial NBS consistent with S-trait to follow-up at 6 months �  Social:

�  Discharged home to mother with LOS 29 days �  DHS involved

References Aschner, J. L, Gien, J., Ambalavan, N., Kinsella, J. P., Konduri, G. G., Lakshminrusimha, S., … Steinhorn, R. H. (2016). Journal of Perinatology, 36, 532-536.

Becquet, O., Bonnet, D., Ville, Y., Allegart, K., & Lapillonne, A. (2018). Paracetamol/acetaminophen during pregnancy induces prenatal ductus arteriosus closure. Pediatrics, 142(1), 1-4.

Delaney, C. & Cornfield, D. N. (2012). Risk factors for persistent pulmonary hypertension of the newborn. Pulmonary Circulation, 2(1), 15-20.

Klein, J. M. (n.d.). Treatment of pulmonary Hypertension. Retrieved from: https://uichildrens.org/health-libraray/treatment-pulmonary-hypertension

Lakshminrusimha, S., Konduri, G. G., & Steinhonrn, R. H. (2016). Considerations in the management of hypoxemic respiratory failure and persistent pulmonary hypertension in term and late preterm neonates. Journal of Perinatology, 36, 512-519.

Lakshminrusimha, S., Matthew, B, & Leach, C. L.. (2016). Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide. Seminars in Perinatology, 40(3), 160-173.

References Lakshminrusimha, S. & Saugstad, O. D. (2016). The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy. Journal of Perinatology, 36, S3-S11.

Lopes, L. L., Carvalho Carrilho, M., Viera Francisco, R. P., Borges Lopes, M. A., Jornada Krebs, V. L., & Zugaib, M. (2016). Fetal ducts arteriosus constriction and closure: analysis of the causes of perinatal outcome related to 45 consecutive cases. Journal of Maternal-Fetal & Neonatal Medicine, 29(4), 638-645.

Pederson, J., Hedegaard, E. R., Simonsen, U., Kruger, M., Infanger, M., & Grimm, D. (2018). Current and future treatments for persistent pulmonary hypertension in the newborn. Basic & Clinical Pharmacology & Toxicology, 123(4), 392-406.

University of Kansas. (1996). Persistent fetal circulation diagram.