Preliminary Study on Neurodevelopmental Outcome and Placental Pathology among Extremely Low Birth Weight Infants

Seong-Hee Oh; Jong-jae Kim; Hyun-jeong Do; Byong Sop Lee; Ki-Soo Kim; Ellen Ai-Rhan Kim

doi:10.14734/kjp.2015.26.1.67

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Oh, Kim, Do, Lee, Kim, and Kim: Preliminary Study on Neurodevelopmental Outcome and Placental Pathology among Extremely Low Birth Weight Infants

Original Article

Korean J Perinatol 2015;26(1):67-77.

Published online: 20 March 2015

DOI: https://doi.org/10.14734/kjp.2015.26.1.67

Preliminary Study on Neurodevelopmental Outcome and Placental Pathology among Extremely Low Birth Weight Infants

Seong-Hee Oh, M.D.¹, Jong-jae Kim, M.D., Ph.D.², Hyun-jeong Do, M.D.¹, Byong Sop Lee, M.D., Ph.D.¹, Ki-Soo Kim, M.D., Ph.D.¹, Ellen Ai-Rhan Kim, M.D., Ph.D.^1,

¹Division of Neonatology, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea

²Department of Pathology, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Ellen Ai-Rhan Kim, M.D., Division of Neona tology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, South Korea Tel: +82-2-3010-3382, Fax: +82-2-3010-6978, E-mail: arkim@amc.seoul.kr

Received 17 February 2015 Revised 28 February 2015 Accepted 28 February 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To investigate the relationship between placental pathology and neurodevelopmental outcomes among extremely low birth weight (ELBW) infants

Methods

Pathology of placentas from ELBW infants born at a tertiary neonatal intensive care unit from January 2007 to December 2012 were reviewed and placental histology was grouped into 3 categories by a designated pathologist: acute chorioamnionitis (ACA), maternal vascular underperfusion (MVU), and control group. Matched ELBW infants were tested for significant neurodevelopmental delays defined as mental developmental index (MDI) or psychomotor developmental index (PDI) <70, using Bayley Scales of Infant Development-II (BSID-II).

Results

The mean gestational age and birth weight of 175 infants were 27.1±2.5 weeks and 764.7±152.3 g respectively. Placental histology revealed MVU (48.0%), ACA (25.1%) and control (26.9%) in distribution. There were less significant patent ductus arteriosus in MVU group than in control group [adjusted odds ratio (OR)=0.331, P=0.011]. The frequencies of other neonatal diseases and mortality were similar in 3 groups. Sixty four of 175 infants were examined for BSID-II at mean corrected 19.9±3.2 months. MVU was associated with significant mental developmental delay (OR=5.185, P=0.036), but after adjustment for head circumference/weight at birth, the statistically significance of association disappeared (adjusted OR=4.391, P=0.075). ACA did not affect neonatal and neurodevelopmental outcomes.

Conclusion

The result of placenta biopsy could be a useful tool in counseling parents for future neurode-velopmental outcome, however, further studies are required to define definitive association in between placenta biopsy and neurodevelopmental outcomes.

Keywords: Placenta, Chorioamnionitis, Underperfusion, Neurodevelopmental, Extremely low birth weight

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Fig. 1.

Light microscopic findings of placental lesions. (A)-(C) compatible with amniotic fluid infection. (A) Umbilical vasculitis, a classical fetal inflammatory response (H-E stain, x100). (B) Necrotizing funisitis showing diffuse band of neutrophil debris in the Wharton's jelly (X40). (C) Acute chorioamnionitis of the chorioamniotic membranes, indicative of maternal inflammatory response. There is diffuse infiltration of the maternal neutrophils into the amnion (X200). Figure D-F compatible with maternal vascular underperfusion. (D) Increased syncytial knots. Almost every chorionic villus has syncytial knots (X100). (E) Acute villous infarct showing coagulation necrosis (X100). (F) Increased intervillous fibrin (X100).

Table 1.

Perinatal characteristics

Characteristics	Control (n=47)	ACA (n=44)	MVU (n=84)	P-value
Gestational age (weeks)^∗	26.4±2.3	25.6±1.2	28.2±2.6	<0.001
Birth weight (g)^∗	766.5±139.2	816.9±121.0	736.4±167.4	0.035
SGA, n (%)	13 (26.5)	0 (0)	51 (60.7)	<0.001
HC (cm)^∗	23.8±1.5	23.6±1.8	24.3±2.0	0.025
HC <10p, n (%)	12 (25.0)	4 (9.5)	44 (53.0)	<0.001
HC/weight (cm/g X100)^∗	3.2±0.5	2.9±0.3	3.4±0.8	<0.001
Male, n (%)	23 (48.9)	21 (47.7)	52 (61.9)	0.211
Multiple gestation, n (%)	31 (63.3)	17 (38.6)	30 (35.7)	0.002
Apgar score at 1min^∗	3.5±1.7	3.2±1.5	3.9±2.0	0.099
Apgar score at 5mins^∗	5.8±1.5	5.4±1.4	6.3±1.8	0.002
Initial pH^∗	7.2±0.1	7.2±0.1	7.2±0.1	0.325
Initial base deficit (mmEq/L)^∗	6.0±4.4	7.3±5.0	6.8±5.0	0.462
Lactic acid (mmol/L)^∗	4.6±2.9	4.3±2.8	5.8±3.7	0.064
Cesarean delivery, n (%)	28 (57.1)	14 (31.8)	72 (85.7)	<0.001
PPROM > 18hrs, n (%)	7 (14.3)	17 (38.6)	9 (10.7)	<0.001
Oligohydramnios	5 (10.6)	1 (2.3)	13 (15.5)	0.079
PIH, n (%)	2 (4.1)	1 (2.3)	28 (33.3)	<0.001
Gestational diabetes, n (%)	2 (4.3)	0 (0)	2 (2.4)	0.474
Antenatal corticosteroid, n (%)	27 (55.1)	25 (56.8)	53 (63.1)	0.789
Maternal age (years)^∗	31.0±4.2	33.3±3.3	31.5±4.2	0.017
Maternal education (College)	37 (78.7)	36 (81.8)	61 (72.6)	0.473
Placental weight (g)^∗,†	211.7±69.5	249.6±92.6	203.6±79.9	0.011
Placental weight<10p, n (%)^†	8 (53.3)	10 (37.0)	51 (80.9)	<0.001
Birth weight/placental weight (g/g)^∗,†	3.9±1.4	3.6±1.0	4.2±1.3	0.170

Abbreviations: ACA, acute chorioamnionitis; MVU, maternal vascular underperfusion; SGA, small for gestational age; HC, head circumference; PPROM, preterm premature rupture of membrane; PIH, pregnancy-induced hypertension.

^∗ Data are given as mean ± standard deviation.

^† One hundred five placentas of 175 infants were checked for placental weights excluding fused placentas of twins.

Table 2.

Perinatal mortality and morbidity among neonates with acute chorioamnionitis and maternal vascular underperfusion

	ACA				MVU
	Odds ratio	95%	% CI	P-value^∗	Odds ratio	95%	% CI	P-value^∗
Mortality	1.150	0.379	3.491	0.805	2.139	0.741	6.173	0.160
PDA	0.468	0.190	1.151	0.098	0.331	0.141	0.778	0.011
NEC	0.648	0.234	1.789	0.402	0.598	0.204	1.750	0.348
Early sepsis	1.421	0.218	9.285	0.714	2.257	0.359	14.202	0.386
Late sepsis	0.962	0.385	2.403	0.934	0.561	0.235	1.341	0.193
IVH	0.715	0.234	2.185	0.556	0.861	0.284	2.605	0.791
PVL	2.430	0.549	10.753	0.242	0.944	0.168	5.312	0.948
ROP	1.916	0.579	6.334	0.287	1.688	0.478	5.965	0.416
BPD	0.382	0.129	1.131	0.082	0.801	0.297	2.159	0.662

Abbreviations: ACA, acute chorioamnionitis; MVU, maternal vascular underperfusion; CI, confidence interval; PDA, patent ductus arteriosus; NEC, necrotizing enterocolitis; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; ROP, retinopathy of prematurity; BPD, bronchopulmonary dysplasia

^∗ Adjusted by gestational age and birth weight

Table 3.

Comparisons of neurodevelopmental delay based on the placental pathology

Developmental index	Control (n=18, 28.1%)	ACA (n=13, 20.3%)	MVU (n=33, 51.6%)	P-value
MDI<85 (n=36, 56.3%)	8 (44.4%)	4 (30.8%)	24 (72.7%)	0.018
PDI<85 (n=32, 50.0%)	10 (55.6%)	5 (38.5%)	17 (51.5%)	0.713
70≤MDI<85 (n=18, 28.1%)	5 (27.8%)	4 (30.8%)	9 (27.3%)	1.000
70≤PDI<85 (n=13, 20.3%)	4 (22.2%)	3 (23.1%)	6 (18.2%)	0.846
MDI<70 (n=18, 28.1%)	3 (16.7%)	0 (0.0%)	15 (45.5%)	0.003
PDI<70 (n=19, 29.7%)	6 (33.3%)	2 (15.4%)	11 (33.3%)	0.476

Abbreviations: ACA, acute chorioamnionitis; MVU, maternal vascular underperfusion; MDI, mental developmental index PDI, psychomotor developmental index

Table 4.

Neurodevelopmental outcome among neonates with acute chorioamnionitis or maternal vascular underperfusion

Developmental index	Placental pathology	Odds ratio	95% C.I.	P-value
70≤MDI<85	Control	1		0.277
	ACA	0.889	0.181 4.375	0.885
	MVU	2.222	0.547 9.023	0.264
MDI<70	Control	1
	ACA	Infinite	0.993
	MVU	5.185	1.114 24.142	0.036
70≤PDI<85	Control	1		0.694
	ACA	0.444	0.063 3.112	0.414
	MVU	0.750	0.163 3.441	0.711
PDI<70	Control	1
	ACA	0.296	0.046 1.908	0.200
	MVU	0.917	0.248 3.389	0.896

Abbreviations: CI, confidence interval; MDI, mental developmental index; PDI, psychomotor developmental index, ACA, acute chorioamnionitis; MVU, maternal vascular underperfusion

Table 5.

Neurodevelopmental outcome among neonates with acute chorioamnionitis or maternal vascular underperfusion after multivariable logistic regression

Developmental index	Placental pathology	Odds ratio	95% CI	P-value^∗
70≤MDI<85	Control	1
	ACA	1.931	0.325 11.476	0.469
	MVU	1.845	0.398 8.558	0.434
MDI<70	Control	1
	ACA	Infinite	0.963
	MVU	4.391	0.863 22.357	0.075
70≤PDI<85	Control	1
	ACA	0.619	0.082 4.660	0.641
	MVU	0.581	0.118 2.869	0.505
PDI<70	Control	1
	ACA	0.533	0.075 3.788	0.529
	MVU	0.620	0.147 2.612	0.515

Abbreviations: CI, confidence interval; MDI, mental developmental index; PDI, psychomotor developmental index, ACA, acute chorioamnionitis; MVU, maternal vascular underperfusion

^∗ Adjusted for head circumference/birth weight

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