Documente Academic
Documente Profesional
Documente Cultură
Neurodevelopmental outcomes of very low birth weight and extremely low birth
weight infants at 18 months of corrected age associated with prenatal risk factors
Shunsuke Tamaru a, Akihiko Kikuchi a,, Kimiyo Takagi a, Masao Wakamatsu a, Kyoko Ono a,
Tsuguhiro Horikoshi a, Hideki Kihara b, Tomohiko Nakamura c
a
b
c
Department of Obstetrics, Center for Perinatal Medicine, Nagano Children's Hospital, Nagano, Japan
Department of Rehabilitation, Nagano Children's Hospital, Nagano, Japan
Deparment of Neonatology, Center for Perinatal Medicine, Nagano Children's Hospital, Nagano, Japan
a r t i c l e
i n f o
Article history:
Received 20 August 2010
Received in revised form 13 October 2010
Accepted 26 October 2010
Keywords:
Extremely low birth weight infant
Kyoto Scale of Psychological Development
Neurodevelopmental outcome
Prenatal risk factor
Very low birth weight infant
a b s t r a c t
Background: Very premature infants occasionally have neurodevelopmental disabilities. However, there have
been quite limited data on prenatal risk factors associated with their neurodevelopmental outcomes.
Aim: To clarify the relationship between prenatal risk factors and neurodevelopmental outcomes of very
premature infants.
Study design: The study design is a retrospective review.
Subjects: One hundred seventy Japanese women with a singleton pregnancy and their infants whose birth
weight being less than 1500 g were included. We classied those infants into 118 appropriate for gestational
age (AGA) and 52 small for gestational age (SGA) infants.
Outcome measures: Infants' neurodevelopmental outcomes at 18 months of corrected age were evaluated by
the Kyoto Scale of Psychological Development 2001 (KSPD). We analyzed and compared the infants'
outcomes and prenatal risk factors between two groups.
Results: Mortality and rate of infants unevaluable by KSPD because of severe impairment were not
signicantly different between those groups. However, the developmental quotient score of the cognitive
adaptive area in SGA infants born between 25 and 31 weeks of gestation was signicantly lower than that in
AGA infants randomly selected as gestation-matched controls. More advanced gestational age and heavier
birth weight protected against adverse neurodevelopmental outcomes in both groups. Moreover, male infants
were related to the excess risk of adverse neurodevelopmental outcomes in the SGA group.
Conclusion: In view of the neurodevelopment of the infants, it seems that the most efcient obstetric strategy
for improving prognosis of premature infants should be targeted to prolong the pregnancy period as long as
the reassuring fetal status and maternal stable health condition are being conrmed.
2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
In the last decade, improvements in perinatal care have resulted in
increased survival rates of very preterm and/or very low birth weight
(VLBW) infants. However, new social and health problems related to
their high risk of brain damage and neurological sequelae have arisen
[1]. Long-term follow-up studies have also emphasized the occurrence
of signicant neuropsychological and behavioral decits at school age of
those who survive without major neurological decits [2]. Moreover,
some studies point out that the problems such as academic under
achievement, behavioral problems, and decits in higher-order neuro-
56
P value
944.5 (4351474)
26.9 (22.031.6)
882.5 (2971480)
30.4 (22.934.7)
0.311
b 0.001
30.4 4.5
60 (50.9%)
65 (55.1%)
9 (7.6%)
31.3 4.6
23 (44.2%)
47 (90.4%)
8 (15.4%)
0.243
0.426
b 0.001
0.12
3 (2.5%)
1 (1.9%)
0.806
106 (89.8%)
43 (82.7%)
0.192
KSPD, the Kyoto Scale of Psychological Development 2001; AGA, appropriate for
gestational age; SGA, small for gestational age; Data are presented as mean standard
deviation, median (range) or number (percentage).
a
MannWhitney test.
b
Student t test.
c
2 test.
Table 3
The KSPD scores of 38 AGA and 19 SGA infants born between 25 and 31 weeks of
gestation that were randomly selected as gestation-matched controls.
P value
27.8 (2531.6)
28 (2531.7)
0.576
7 (8.1%)
4 (12.9%)
0.204
2 (2.3%)
1 (3.2%)
0.786
79 (91.9%)
26 (83.9%)
0.209
KSPD, the Kyoto Scale of Psychological Development 2001; AGA, appropriate for
gestational age; SGA, small for gestational age; data are presented as median (range) or
number (percentage).
a
MannWhitney test.
b
2 test.
P value
92.5 (31118)
95.8 14.4
95.3 16.3
94.4 13.7
87.3 (64112)
87.2 13.4
93.7 17.7
88.4 14.1
0.436
0.034
0.738
0.131
KSPD, the Kyoto Scale of Psychological Development 2001; AGA, appropriate for
gestational age; SGA, small for gestational age; data are presented as mean standard
deviation or median (range).
a
MannWhitney test.
b
Student t test.
Table 2
Characteristics of the study population born between 25 and 31 gestational weeks.
AGA group (n= 86)
57
Normal
development
(n= 68)
Poor
Borderline
development prognosis
(n= 25)
(n = 25)
27.6 2.3
1051.3273.2
33/68 (48.5)
32/68 (47.1)
49/66 (74.2)
32/66 (48.5)
9/68 (13.2)
26.5 2.2
901.2271.5
12/25 (48)
13/25 (52)
18/25 (72)
13/25 (52)
7/25 (28)
P value
25.3 2.0
b0.001
738.2200.3 b0.001
15/25 (60)
0.587
15/25 (60)
0.537
21/25 (84)
0.548
12/25 (48)
0.948
5/25 (20)
0.243
AGA, appropriate for gestational age; PROM, preterm rupture of membranes; CAM,
chorioamnionitis; NRFS; non-reassuring fetal status; ANOVA, analysis of variance; data
are presented as mean standard deviation or number (percentage).
a
One-way factorial ANOVA.
b
2 test.
c
Presence of CAM and funisitis were not investigated in two cases of normal
development group.
58
Table 5
Prognosis of 52 infants at 18 months of corrected age and prenatal risk factors in SGA group.
Normal development
(n = 30)
Borderline development
(n = 10)
Poor prognosis
(n = 12)
P Value
31.1 2.8
1022.5320.8
2.23 0.87
8/30 (26.7)
7/28 (25)
23/30 (76.7)
21/30 (70)
6/30 (20)
20/30 (66.7)
28.9 2.6
911.4267.7
1.74 0.8
8/10 (80)
2/6 (33.3)
3/10 (30)
4/10 (40)
1/10 (10)
5/10 (50)
26.5 3.4
582.3277.8
1.98 1.17
7/12 (58.3)
4/9 (44.4)
4/12 (33.3)
8/12 (66.7)
5/10 (50)
7/10 (70)
b0.001
b0.001
0.335
0.007
0.535
0.005
0.225
0.08
0.577
SGA, small for gestational age; SD, standard deviation; EFW, estimated fetal weight; PIH, pregnancy-induced hypertension; NRFS, non-reassuring fetal status; AREDFV, absent or
reversed end-diastolic ow velocity; UA, umbilical artery; RI, resistance index; MCA, middle cerebral artery; ANOVA, analysis of variance; data are presented as mean standard
deviation or number (percentage).
a
One-way factorial ANOVA.
b
2 test.
c
Nine cases of PROM were excluded from the data.
d
Presence of AREDFV in UA and RI ratio (RI of MCA/UA) were not investigated in two cases of poor prognosis group.
59
[2] Marlow N, Wolke D, Bracewell MA, Samara M, EPICure Study Group. Neurologic
and developmental disability at six years of age after extremely preterm birth. N
Engl J Med 2005;352:919.
[3] Hille ET, Weisglas-Kuperus N, van Goudoever JB, Jacobusse GW, Ens-Dokkum MH,
de Groot L, et al. Functional outcomes and participation in young adulthood for
very preterm and very low birth weight infants: the Dutch Project on Preterm and
Small for Gestational Age Infants at 19 years of age. Pediatrics 2007;120:e58795.
[4] Hack M, Youngstrom EA, Cartar L, Schluchter M, Taylor HG, Flannery D, et al.
Behavioral outcomes and evidence of psychopathology among very low birth
weight infants at age 20 years. Pediatrics 2004;114:93240.
[5] Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from
infancy to adulthood. Lancet 2008;371:2619.
[6] Yoon BH, Romero R, Park JS, Kim M, Oh SY, Kim CJ, et al. The relationship among
inammatory lesions of the umbilical cord (funisitis), umbilical cord plasma
interleukin 6 concentration, amniotic uid infection, and neonatal sepsis. Am J
Obstet Gynecol 2000;183:11249.
[7] Hagberg H, Wennerholm UB, Svman K. Sequelae of chorioamnionitis. Curr Opin
Infect Dis 2002;15:3016.
[8] Wu YW, Colford Jr JM. Chorioamnionitis as a risk factor for cerebral palsy: a metaanalysis. JAMA 2000;284:141724.
[9] Suppiej A, Franzoi M, Vedovato S, Marucco A, Chiarelli S, Zanardo V. Neurodevelopmental outcome in preterm histological chorioamnionitis. Early Hum Dev
2009;85:1879.
[10] Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm
delivery. N Engl J Med 2000;342:15007.
[11] Gray PH, Jones P, O'Callaghan MJ. Maternal antecedents for cerebral palsy in
extremely preterm babies: a casecontrol study. Dev Med Child Neurol 2001;43:
5805.
[12] Spinillo A, Montanari L, Bergante C, Gaia G, Chiara A, Fazzi E. Prognostic value of
umbilical artery Doppler studies in unselected preterm deliveries. Obstet Gynecol
2005;105:61320.
[13] McCormick MC, Workman-Daniels K, Brooks-Gunn J. The behavioral and
emotional well-being of school-age children with different birth weights.
Pediatrics 1996;97:1825.
[14] Schothorst PF, van Engeland H. Long-term behavioral sequelae of prematurity.
J Am Acad Child Adolesc Psychiatry 1996;35:17583.
[15] Pryor J, Silva PA, Brooke M. Growth, development and behaviour in adolescents
born small-for-gestational-age. J Paediatr Child Health 1995;31:4037.
[16] Geva R, Eshel R, Leitner Y, Fattal-Valevski A, Harel S. Memory functions of children
born with asymmetric intrauterine growth restriction. Brain Res 2006;1117:18694.
[17] Geva R, Eshel R, Leitner Y, Valevski AF, Harel S. Neuropsychological outcome of
children with intrauterine growth restriction: a 9-year prospective study.
Pediatrics 2006;118:91100.
[18] O'Keeffe MJ, O'Callaghan M, Williams GM, Najman JM, Bor W. Learning, cognitive,
and attentional problems in adolescents born small for gestational age. Pediatrics
2003;112:3017.
[19] Feldman R, Eidelman AI. Neonatal state organization, neuromaturation, motherinfant interaction, and cognitive development in small-for-gestational-age
premature infants. Pediatrics 2006;118:e86978.
[20] Walker DM, Marlow N. Neurocognitive outcome following fetal growth
restriction. Arch Dis Child Fetal Neonatal Ed 2008;93:F3225.
[21] Ogawa Y, Iwamura T, Kuriya N, Nishida H, Takeuchi H, Takada M, et al. Birth size
standards by gestational age for Japanese neonates. Acta Neonat Jap 1998;34:
62432 (in Japanese).
[22] Uesugi M, Tokuhisa K, Shimada T. The reliability and validity of the Alberta Infant
Motor Scale in Japan. J Phys Ther Sci 2008;20:16975.
[23] Koyama T, Osada H, Tsujii H, Kurita H. Utility of the Kyoto Scale of Psychological
Development in cognitive assessment of children with pervasive developmental
disorders. Psychiatry Clin Neurosci 2009;63:2413.
[24] Blanc WA. Pathology of the placenta, membranes and umbilical cord in bacterial,
fungal and viral infections in man. In: Naeye RL, Kissane JM, Kaufman N, editors.
Perinatal Diseases. Baltimore, MD: Williams & Wilkins; 1981. p. 67132.
[25] Shinozuka N, Akamatsu N, Sato S, Kanzaki T, Takeuch H, Natori M, et al. Ellipse
tracing fetal growth assessment using abdominal circumference: JSUM standardization committee for fetal measurements. J Med Ultrasound 2000;8:8794.
[26] Shinozuka N. Fetal biometry and fetal weight estimation: JSUM standardization.
Ultrasound Rev Obst Gynecol 2002;2:15661.
[27] Mishina J. Protocols for follow-up of high-risk infants. Perinat Med 2000;30:
126372 (in Japanese).
[28] Procianoy RS, Koch MS, Silveira RC. Neurodevelopmental outcome of appropriate and
small for gestational age very low birth weight infants. J Child Neurol 2009;24:
78894.
[29] Spinillo A, Montanari L, Gardella B, Roccio M, Stronati M, Fazzi E. Infant sex,
obstetric risk factors, and 2-year neurodevelopmental outcome among preterm
infants. Dev Med Child Neurol 2009;51:51825.
[30] Johnston MV, Hagberg H. Sex and the pathogenesis of cerebral palsy. Dev Med
Child Neurol 2007;49:748.
[31] Cheng SW, Chou HC, Tsou KI, Fang LJ, Tsao PN. Delivery before 32 weeks of
gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome. Early Hum Dev 2004;76:3946.
[32] American College of Obstetricians Gynecologists Committee on Obstetric Practice.
Society for MaternalFetal Medicine. Committee Opinion No. 455: Magnesium
sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol
2010;115:66971.