The role of the placenta in perinatal asphyxia, neonatal encephalopathy, and neurodevelopmental outcome: A review

Constant Ndjapa-Ndamkou, Logie Govender, Shastra Bhoora, Lawrence Chauke

Abstract

Perinatal asphyxia contributes significantly to neonatal deaths globally. This may occur due to the effects of various phenomena like uterine rupture, infections, maternal hemodynamic compromise (amniotic fluid embolus), placenta, and umbilical cord (umbilical cord knot, placental abruption, or compression). Perinatal asphyxia is the term used for interrupted blood flow or the exchange of gases in the fetus during the prenatal period. The reduced oxygenation induces a cascade of brain injuries, resulting in long-term damage to the infant’s brain. Some infants exposed to perinatal hypoxia-ischemia will make an immediate recovery and have normal survival, while others may suffer from an evolving clinical encephalopathy. This review article focuses on the relationship between the placenta, neonatal encephalopathy, and neurodevelopmental outcome. It also aims to identify possible interventions and drive the focus of policymakers towards issues that evolve around perinatal asphyxia, neonatal encephalopathy, and neonatal care and that have a high impact on infant morbidity in sub-Saharan Africa. (Afr J Reprod Health 2023; 27 [1]: 107- 118).

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Lee Anne CC, Katz Joanne, Blencowe Hannah, Cousens

Simon, Kozuki Naoko, Vogel Joshua P, Adair

Linda, Baqui Abdullah H, Bhutta Zulfiqar A,

Caulfield Laura E, Christian Parul, Clarke Siân E,

Ezzati Majid, Fawzi Wafaie, Gonzalez Rogelio,

Huybregts Lieven, Kariuki Simon, Kolsteren

Patrick, Lusingu John, Marchant Tanya, Merialdi

Mario, Mongkolchati Aroonsri, Mullany Luke C,

Ndirangu James, Newell Marie-Louise, Nien Jyh

Kae, Osrin David, Roberfroid Dominique, Rosen

Heather E, Sania Ayesha, Silveira Mariangela F,

Tielsch James, Vaidya Anjana, Willey Barbara A,

Lawn Joy E and Black Robert E. National and

regional estimates of term and preterm babies born

small for gestational age in 138 low-income and

middle-income countries in 2010. Lancet Glob Heal.

;1(1):e26-e36. doi:10.1016/S2214-

X(13)70006-8

Liu L, Oza S, Hogan D, Liu L, Oza S, Hogan D, Chu Y,

Perin J, Zhu J, Lawn JE, Cousens S, Mathers C and

Black RE. Global, regional, and national causes of

under-5 mortality in 2000–15: an updated systematic

analysis with implications for the Sustainable

Development Goals. Lancet.

;388(10063):3027-3035. doi:10.1016/S0140-

(16)31593-8

Biselele T, Naulaers G, Bunga Muntu P, Nkidiaka E,

Kapepela M, Mavinga L and Tady BA Descriptive

Study of Perinatal Asphyxia at the University

Hospital of Kinshasa (Democratic Republic Of

Congo). J Trop Pediatr. 2013;59(4):274-279.

doi:10.1093/tropej/fmt011

Ahearne CE. Short and long term prognosis in perinatal

asphyxia: An update. World J Clin Pediatr.

;5(1):67. doi:10.5409/wjcp.v5.i1.67

Yadav N and Damke S. Study of risk factors in children with

birth asphyxia. Int J Contemp Pediatr.

;4(2):518. doi:10.18203/2349-

ijcp20170701

Malusi Z, Schubert PT, Theron GB and Wright CA. The

value of histopathology of the placenta in a tertiary

referral hospital in South Africa. S Afr J Obstet

Gynaecol. 2019;25(2):64. doi:10.7196/sajog.1434

Pitaphrom A and Sukcharoen N. Pregnancy outcomes in

placental abruption. J Med Assoc Thai.

;89(10):1572-1578.

Lloyd LG and De Witt W. Neonatal mortality in South

Africa: How are we doing and can we do better?

South African Med J. 2013;103(8):518.

doi:10.7196/SAMJ.7200

Weckman AM, Ngai M, Wright J, McDonald CR and Kain

KC. The Impact of Infection in Pregnancy on

Placental Vascular Development and Adverse Birth

Outcomes. Front Microbiol. 2019;10.

doi:10.3389/fmicb.2019.01924

Burton GJ and Fowden AL. The placenta: a multifaceted,

transient organ. Philos Trans R Soc B Biol Sci.

;370(1663):20140066.

doi:10.1098/rstb.2014.0066

Kapila V and Chaudhry K. Physiology, Placenta.

StatPearls [Internet]. Published online 2021.

Suhag A and Berghella V. Intrauterine Growth Restriction

(IUGR): Etiology and Diagnosis. Curr Obstet

Gynecol Rep. 2013;2(2):102-111.

doi:10.1007/s13669-013-0041-z

Ko H, Dehority W and R. Maxwell J. The Impact of

Maternal Infection on the Neonate. In: Congenital

Anomalies in Newborn Infants - Clinical and

Etiopathological Perspectives. IntechOpen; 2021.

doi:10.5772/intechopen.91637

Watson-Jones D, Changalucha J, Gumodoka B, Weiss H,

Rusizoka M, Ndeki L, Whitehouse A, Balira R,

Todd J, Ngeleja D, Ross D, Anne Buvé, Richard

Hayes and David Mabey. Syphilis in Pregnancy in

Tanzania. I. Impact of Maternal Syphilis on

Outcome of Pregnancy. J Infect Dis.

;186(7):940-947. doi:10.1086/342952

Chico RM, Chaponda EB and Ariti C, Chandramohan D.

Sulfadoxine-Pyrimethamine Exhibits DoseResponse Protection Against Adverse Birth

Outcomes Related to Malaria and Sexually

Transmitted and Reproductive Tract Infections. Clin

Infect Dis. 2017;64(8):1043-1051.

doi:10.1093/cid/cix026

Conroy AL, McDonald CR, Gamble JL, Olwoch P,

Natureeba P, Cohan D, Kamya MR, Havlir DV,

Dorsey G and Kain KC. Altered angiogenesis as a

common mechanism underlying preterm birth, small

for gestational age, and stillbirth in women living

with HIV. Am J Obstet Gynecol.

;217(6):684.e1-684.e17.

doi:10.1016/j.ajog.2017.10.003

McDonald CR, Cahill LS, Ho KT, Yang J, Kim H, Silver KL, Ward PA, Mount HT, Liles WC, Sled JG and

Kain KC. Experimental Malaria in Pregnancy

Induces Neurocognitive Injury in Uninfected

Offspring via a C5a-C5a Receptor Dependent

Pathway. Mota MM, ed. PLOS Pathog.

;11(9):e1005140.

doi:10.1371/journal.ppat.1005140

Griffin JB, Lokomba V, Landis SH, Thorp JM, Herring

AH, Tshefu AK, Rogerson SJ and Meshnick SR.

Plasmodium falciparum parasitaemia in the first half

of pregnancy, uterine and umbilical artery blood

flow, and foetal growth: a longitudinal Doppler

ultrasound study. Malar J. 2012;11(1):319.

doi:10.1186/1475-2875-11-319

Penn AA, Wintermark P, Chalak LF, Armstrong J, Redline

R, Scher MS, Nelson KB, Guidelines NB and

Publications Committee. Placental contribution to

neonatal encephalopathy. Semin Fetal Neonatal

Med. 2021;26(4):101276.

doi:10.1016/j.siny.2021.101276

Simiyu IN, Mchaile DN, Katsongeri K, Philemon RN and

Msuya SE. Prevalence, severity and early outcomes

of hypoxic ischemic encephalopathy among

newborns at a tertiary hospital, in northern Tanzania.

BMC Pediatr. 2017;17(1):131. doi:10.1186/s12887-

-0876-y

Padayachee N and Ballot DE. Outcomes of neonates with

perinatal asphyxia at a tertiary academic hospital in

Johannesburg, South Africa. South African J Child

Heal. 2013;7(3):89. doi:10.7196/sajch.574

McIntyre S, Nelson KB, Mulkey SB, Lechpammer M,

Molloy E and Badawi N. Neonatal encephalopathy:

Focus on epidemiology and underexplored aspects

of etiology. Semin Fetal Neonatal Med.

;26(4):101265.

doi:10.1016/j.siny.2021.101265

Van Bel F and Groenendaal F. Birth asphyxia-induced

brain damage: the long road to optimal reduction and

prevention. Pediatr Med. 2020;3(3).

Aslam S, Strickland T and Molloy EJ. Neonatal

Encephalopathy: Need for Recognition of Multiple

Etiologies for Optimal Management. Front Pediatr.

;7. doi:10.3389/fped.2019.00142

Gillam-Krakauer M and Gowen Jr CW. Birth asphyxia.

Published online 2017.

Stout MJ and Cahill AG. Electronic Fetal Monitoring: Past,

Present, and Future. Clin Perinatol. 2011;38(1):127-

doi:10.1016/j.clp.2010.12.002

Ugwumadu A. Understanding cardiotocographic patterns

associated with intrapartum fetal hypoxia and

neurologic injury. Best Pract Res Clin Obstet

Gynaecol. 2013;27(4):509-536.

doi:10.1016/j.bpobgyn.2013.04.002

Yli BM and Kjellmer I. Pathophysiology of foetal

oxygenation and cell damage during labour. Best

Pract Res Clin Obstet Gynaecol. 2016;30:9-21.

Schneider H. Oxygenation of the placental–fetal unit in

humans. Respir Physiol Neurobiol. 2011;178(1):51-

doi:10.1016/j.resp.2011.05.009

HE Reinebrant,SH Leisher, M Coory, S Henry, AM

Wojcieszek, G Gardener, R Lourie, D Ellwood, Z

Teoh, E Allanson, H Blencowe, ES Draper, JJ

Erwich,JF Frøen, J Gardosi, K Gold, S Gordijn, A

Gordon, AEP Heazell, TY Khong, F Korteweg, JE

Lawn, EM McClure, J Oats, R Pattinson, K

Pettersson, D Siassakos, RM Silver, GCS Smith, Ö

Tunçalp and V Flenady. Making stillbirths visible: a

systematic review of globally reported causes of

stillbirth. BJOG An Int J Obstet Gynaecol.

;125(2):212-224. doi:10.1111/1471-

14971

MacLennan AH, Thompson SC and Gecz J. Cerebral

palsy: causes, pathways, and the role of genetic

variants. Am J Obstet Gynecol. 2015;213(6):779-

doi:10.1016/j.ajog.2015.05.034

Alfirevic Z, Devane D and Gyte GML. Continuous

cardiotocography (CTG) as a form of electronic fetal

monitoring (EFM) for fetal assessment during

labour. Cochrane database Syst Rev. 2013;(5).

Ayres-de-Campos D, Spong CY and Chandraharan E.

FIGO consensus guidelines on intrapartum fetal

monitoring: Cardiotocography. Int J Gynecol

Obstet. 2015;131(1):13-24.

doi:10.1016/j.ijgo.2015.06.020

Liston R, Sawchuck D and Young D. No. 197b-Fetal

Health Surveillance: Intrapartum Consensus

Guideline. J Obstet Gynaecol Canada.

;40(4):e298-e322.

doi:10.1016/j.jogc.2018.02.011

National Collaborating Centre for Women’s and

Children’s Health (UK). Intrapartum care: care of

healthy women and their babies during childbirth.

Published online 2014.

Paterno MT, McElroy K and Regan M. Electronic Fetal

Monitoring and Cesarean Birth: A Scoping Review.

Birth. 2016;43(4):277-284. doi:10.1111/birt.12247

Kallianidis AF, Schutte JM, van Roosmalen J and van den

Akker T. Maternal mortality after cesarean section

in the Netherlands. Eur J Obstet Gynecol Reprod

Biol. 2018;229:148-152.

doi:10.1016/j.ejogrb.2018.08.586

Esteves-Pereira AP, Deneux-Tharaux C, NakamuraPereira M, Saucedo M, Bouvier-Colle M-H and Leal

M do C. Caesarean Delivery and Postpartum

Maternal Mortality: A Population-Based Case

Control Study in Brazil. Leone T, ed. PLoS One.

;11(4):e0153396.

doi:10.1371/journal.pone.0153396

Small KA, Sidebotham M, Fenwick J and Gamble J.

Intrapartum cardiotocograph monitoring and

perinatal outcomes for women at risk: Literature

review. Women and Birth. 2020;33(5):411-418.

doi:10.1016/j.wombi.2019.10.002

Ravichandran L, Allen VM, Allen AC, Vincer M, Baskett

TF and Woolcott CG. Incidence, Intrapartum Risk

Factors, and Prognosis of Neonatal HypoxicIschemic Encephalopathy Among Infants Born at 35

Weeks Gestation or More. J Obstet Gynaecol

Canada. 2020;42(12):1489-1497.

doi:10.1016/j.jogc.2020.04.020

Thayyil S, Pant S, Montaldo P, Thayyil S, Pant S,

Montaldo P, Shukla D, Oliveira V, Ivain P, Bassett

P, Swamy R, Mendoza J, Moreno-Morales M, Lally

PJ, Benakappa N, Bandiya P, Shivarudhrappa I,

Somanna J, Kantharajanna UB, Rajvanshi A,

Krishnappa S, Joby PK, Jayaraman K Chandramohan RA, Kamalarathnam CN, Sebastian

M, Tamilselvam I, Rajendran U, Soundrarajan R,

Kumar V, Sudarsanan H, Vadakepat P, Gopalan K,

Sundaram M, Seeralar A, Vinayagam P, Sajjid M,

Baburaj M, Murugan KD, Sathyanathan BP,

Kumaran ES, Mondkar J, Manerkar S, Joshi AR,

Dewang K, Bhisikar SM, Kalamdani P, Bichkar V,

Patra S, Jiwnani K, Shahidullah M, Moni SC, Jahan

I, Mannan MA, Dey SK, Nahar N, Islam MN,

Shabuj KH, Rodrigo R, Sumanasena S,

Abayabandara-Herath T, Chathurangika GK,

Wanigasinghe J, Sujatha R, Saraswathy S, Rahul A,

Radha SJ, .Sarojam MK, Krishnan V, Nair MK,

Devadas S, Chandriah S, Venkateswaran H, Burgod

C, Chandrasekaran M, Atreja G, Muraleedharan P,

Herberg JA, 'Kling'Chong WK, Sebire NJ, Pressler

R, Ramji S and Shankaran S. HT for moderate or

severe neonatal encephalopathy in low-income and

middle-income countries (HELIX): a randomised

controlled trial in India, Sri Lanka, and Bangladesh.

Lancet Glob Heal. 2021;9(9):e1273-e1285.

doi:10.1016/S2214-109X(21)00264-3

Buchmann EJ, Pattinson RC and Nyathikazi N.

Intrapartum-related birth asphyxia in South Africa

lessons from the first national perinatal care survey.

South African Med J. 2002;92(11):897-901.

Masaba BB and Mmusi-Phetoe R. Neonatal Survival in

Sub-Sahara: A Review of Kenya and South Africa.

J Multidiscip Healthc. 2020;Volume 13:709-716.

doi:10.2147/JMDH.S260058

Bracci R, Perrone S and Buonocore G. The Timing of

Neonatal Brain Damage. Neonatology.

;90(3):145-155. doi:10.1159/000092517

Wachtel E V and Hendricks-Muñoz KD. Current

Management of the Infant Who Presents with

Neonatal Encephalopathy. Curr Probl Pediatr

Adolesc Health Care. 2011;41(5):132-153.

doi:10.1016/j.cppeds.2010.12.002

Ezenwa B, Ezeaka C, Fajolu I, Ogbenna A, Olowoyeye O,

Nwaiwu O, Opoola Z and Olorunfemi G. Impact of

Erythropoietin in the management of Hypoxic

Ischaemic Encephalopathy in resource-constrained

settings: protocol for a randomized control trial.

BMC Neurol. 2020;20(1):171. doi:10.1186/s12883-

-01751-y

Miller SP, Ramaswamy V, Michelson D, Barkovich AJ,

Holshouser B, Wycliffe N, Glidden DV, Deming D,

Partridge JC, Wu YW, Ashwal S, and Donna

M.Ferriero. Patterns of brain injury in term neonatal

encephalopathy. J Pediatr. 2005;146(4):453-460.

doi:10.1016/j.jpeds.2004.12.026

Enweronu-Laryea CC, Adedemy J-D, Okonkwo IR, Lee

ACC and Robertson NJ. International Perspectives:

Birth-Associated Neonatal Encephalopathy:

Postresuscitation Care in West African Newborns.

Neoreviews. 2018;19(9):e507-e515.

doi:10.1542/neo.19-9-e507

Hoque M, Haaq S and Islam R. Causes of neonatal

admissions and deaths at a rural hospital in

KwaZulu-Natal, South Africa. South African J

Epidemiol Infect. 2011;26(1):26-29.

Parikh P and Juul SE. Neuroprotection Strategies in

Preterm Encephalopathy. Semin Pediatr Neurol.

;32:100772. doi:10.1016/j.spen.2019.08.008

Tann CJ, Nakakeeto M, Willey BA, Sewegaba M, Webb

EL, Oke I, Mutuuza ED, Peebles D, Musoke M,

Harris KA, Sebire NJ, Nigel Klein, Jennifer J

Kurinczuk, Alison M Elliott and Nicola J Robertson.

Perinatal risk factors for neonatal encephalopathy:

an unmatched case-control study. Arch Dis Child -

Fetal Neonatal Ed. 2018;103(3):F250-F256.

doi:10.1136/archdischild-2017-312744

Kali GTJ, Martinez-Biarge M, Van Zyl J, Smith J and

Rutherford M. Management of therapeutic HT for

neonatal hypoxic ischaemic encephalopathy in a

tertiary centre in South Africa. Arch Dis Child -

Fetal Neonatal Ed. 2015;100(6):F519-F523.

doi:10.1136/archdischild-2015-308398

Wilson A, Gallos ID, Plana N, Lissauer D, Khan KS,

Zamora J, MacArthur C and Coomarasamy A.

Effectiveness of strategies incorporating training

and support of traditional birth attendants on

perinatal and maternal mortality: meta-analysis.

BMJ. 2011;343(dec01 1):d7102-d7102.

doi:10.1136/bmj.d7102

Hyder A. The burden of disease from neonatal mortality: a

review of South Asia and Sub-Saharan Africa.

BJOG An Int J Obstet Gynaecol. 2003;110(10):894-

doi:10.1016/S1470-0328(03)02446-7.

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