Placental pathology of neonates diagnosed with encephalopathy soon after birth: A retrospective analytical study
DOI:
https://doi.org/10.7196/SAMJ.2026.v116i6.3811Keywords:
Placental histopathology, Neonatal , EncephalopathyAbstract
Background. Placental pathology has been linked to neonatal encephalopathy (NE). Despite the high prevalence of NE in low- and middle- income countries (LMICs), there are limited published studies exploring this association from LMICs.
Objective. To describe and analyse the histopathology of placentas from neonates diagnosed with encephalopathy shortly after birth.
Methods. A retrospective analytical study was conducted on neonates diagnosed with encephalopathy at Klerksdorp/Tshepong hospital complex, South Africa. Placentas from term and near-term neonates (birthweight ≥2 000 g) diagnosed with encephalopathy within the first 24 hours of life were sent for histopathological examination. Neonates were grouped into those with encephalopathy with or without intrapartum hypoxia (IH) (base deficit ≥12 mmol/L). The severity of NE was assessed as mild, moderate or severe, according to Sarnat staging. The types and extent of placental lesions were compared between those with mild and moderate-to-severe NE, and between cases with or without IH.
Results. Of 16 336 live births, 271 neonates were diagnosed with NE, and of these, 193 (71.2%) had NE with IH. Placental histopathology results were available for 239 neonates (88.2%). The median placental weight was 428 g, with 46.6% of placentas weighing below the 10th percentile. Cord abnormalities were observed in 27.2% of placentas. Nearly all placentas (98.2%) exhibited at least one histopathological lesion. The most common microscopic placental lesions identified were maternal vascular malperfusion (MVM) (55.6%), fetal vascular malperfusion (55.1%), acute chorioamnionitis (41.2%) and villitis of unknown aetiology (28.9%). There was a significant association between NE with IH and the presence of MVM, with an adjusted odds ratio of 3.24 (95% confidence interval 1.19 - 8.79). No significant association was found between the presence or number of different placental lesions and the severity of NE. Factors associated with severity of any NE (with and without IH) included an Apgar score <7 at 10 minutes (p<0.001) and pH <7.00 (p<0.001).
Conclusion. A high proportion of neonates with encephalopathy showed evidence of IH. Approximately half of the placentas were below the 10th percentile in weight, and about a quarter had macroscopic cord abnormalities. Almost all neonates with encephalopathy displayed ≥1 microscopic placental lesion. A strong association was found between the presence of MVM and NE with IH.
References
1. Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: When? Where? Why? Lancet
2005;365(9462):891-900. https://doi.org/10.1016/S0140-6736(05)71048-5
2. Lee ACC, Kozuki N, Blencowe H, et al. Intrapartum-related neonatal encephalopathy incidence
and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res
2013;74(Suppl 1):S50-S72. https://doi.org/10.1038/pr.2013.206
3. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and
hypoxic-ischaemic encephalopathy. Early Hum Dev 2010;86(6):329-338. https://doi.org/10.1016/j.
earlhumdev.2010.05.010
4. Bruckmann EK, Velaphi S. Intrapartum asphyxia and hypoxic ischaemic encephalopathy in a public
hospital: Incidence and predictors of poor outcome. S Afr Med J 2015;105(4):298. https://doi.
org/10.7196/SAMJ.9140
5. Ballot DE, Padayachee N. Outcomes of neonates with perinatal asphyxia at a tertiary hospital in
Johannesburg, South Africa. S Afr J Child Health 2013;7(3):87-94. https://doi.org/doi.org/10.7196/
sajch.574
6. Horn AR, Swingler GH, Myer L, et al. Defining hypoxic ischemic encephalopathy in newborn
infants: Benchmarking in a South African population. J Perinat Med 2013;41(2):211-217. https://doi.
org/10.1515/jpm-2012-0107
7. Vik T, Redline R, Nelson KB, et al. The placenta in neonatal encephalopathy: A case-control study. J
Pediatr 2018;202:77-85.e3. https://doi.org/10.1016/j.jpeds.2018.06.005
8. Khong TY, Mooney EE, Ariel I, et al. Sampling and definitions of placental lesions: Amsterdam
Placental Workshop Group Consensus Statement. Arch Pathology Laboratory Med 2016;140(7):698-
713. https://doi.org/10.5858/arpa.2015-0225-CC
9. Nelson KB, Penn AA. Is infection a factor in neonatal encephalopathy? Arch Dis Child Fetal Neonatal
Ed 2015;100(1):F8-F10. https://doi.org/10.1136/archdischild-2014-306192
10. Mir IN, Johnson-Welch SF, Nelson DB, Brown LS, Rosenfeld CR, Chalak LF. Placental pathology is
associated with severity of neonatal encephalopathy and adverse developmental outcomes following
hypothermia. Am J Obstet Gynecol 2015;213(6):849.e1-7. https://doi.org/10.1016/j.ajog.2015.09.072
11. Bhorat I, Buchmann E, Soma-Pillay P, Nicolaou E, Pistorius L, Smuts I. Cerebral palsy and criteria
implicating acute intrapartum hypoxia in neonatal encephalopathy – an obstetric perspective for
the South African setting. S Afr Med J 2021;111(3b):277-279. https://doi.org/10.7196/SAMJ.2021.
v111i3b.14923
12. O’Heney J, McAllister S, Maresh M, Blott M. Fetal monitoring in labour: Summary and update of NICE
guidance. BMJ 2022;379:o2854. https://doi.org/10.1136/bmj.o2854
13. Thompson CM, Puterman AS, Linley LL, et al. The value of a scoring system for hypoxic ischaemic
encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr 1997;86(7):757-761.
https://doi.org/10.1111/j.1651-2227.1997.tb08581.x
14. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and
electroencephalographic study. Arch Neurol 1976;33(10):696-705. https://doi.org/10.1001/
archneur.1976.00500100030012
15. Viscardi RM, Sun CC. Placental lesion multiplicity: Risk factor for IUGR and neonatal cranial
ultrasound abnormalities. Early Hum Dev 2001;62(1):1-10. https://doi.org/10.1016/s0378-
3782(01)00114-1
16. Moodley J, Onyangunga OA, Maharaj NR. Hypertensive disorders in primigravid black South African
women: A one-year descriptive analysis. Hypertens Pregnancy 2016;35(4):529-535. https://doi.org/10
.1080/10641955.2016.1193190
17. Yang W, Wang L, Tian T, et al. Maternal hypertensive disorders in pregnancy and risk of hypoxicischemia
encephalopathy. J Matern Fetal Neonatal Med 2021;34(11):1754-1762. https://doi.org/10.1
080/14767058.2019.1647529
18. MacLennan A. A template for defining a causal relation between acute intrapartum events and cerebral
palsy: International consensus statement. BMJ 1999;319(7216):1054-1059. https://doi.org/10.1136/
bmj.319.7216.1054
19. Harteman JC, Nikkels PGJ, Benders MJNL, Kwee A, Groenendaal F, de Vries LS. Placental pathology
in full-term infants with hypoxic-ischemic neonatal encephalopathy and association with magnetic
resonance imaging pattern of brain injury. J Pediatr 2013;163(4):968-995.e2. https://doi.org/10.1016/j.
jpeds.2013.06.010
20. Hagberg B, Hagberg G, Beckung E, Uvebrant P. Changing panorama of cerebral palsy in Sweden. VIII.
Prevalence and origin in the birth year period 1991-94. Acta Paediatr 2001;90(3):271-277.
21. Cowan F, Rutherford M, Groenendaal F, et al. Origin and timing of brain lesions in term infants
with neonatal encephalopathy. Lancet 2003;361(9359):736-742. https://doi.org/10.1016/S0140-
6736(03)12658-X
22. Redline RW, O’Riordan MA. Placental lesions associated with cerebral palsy and neurologic
impairment following term birth. Arch Pathol Lab Med 2000;124(12):1785-1791. https://doi.
org/10.5858/2000-124-1785-PLAWCP
23. Nowak C, Joubert M, Jossic F, et al. Perinatal prognosis of pregnancies complicated by placental
chronic villitis or intervillositis of unknown aetiology and combined lesions: About a series of 178
cases. Placenta 2016;44:104-108. https://doi.org/10.1016/j.placenta.2016.04.017
24. Redline RW. Placental pathology: Pathways leading to or associated with perinatal brain injury in
experimental neurology. Special issue: Placental mediated mechanisms of perinatal brain injury. Exp
Neurol 2022;347:113917. https://doi.org/10.1016/j.expneurol.2021.113917
25. Romero R, Kim YM, Pacora P, et al. The frequency and type of placental histologic lesions in term
pregnancies with normal outcome. J Perinat Med 2018;46(6):613-630. https://doi.org/10.1515/jpm-
2018-0055
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