Neurodevelopmental outcomes of very low birth weight and extremely low birth weight infants at 18 months of corrected age associated with prenatal risk factors

doi:10.1016/j.earlhumdev.2010.10.004

Early Human Development

Volume 87, Issue 1, January 2011, Pages 55-59

https://doi.org/10.1016/j.earlhumdev.2010.10.004 Get rights and content

Abstract

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 classified 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 significantly 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 significantly 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 efficient 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 confirmed.

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 significant neuropsychological and behavioral deficits at school age of those who survive without major neurological deficits [2]. Moreover, some studies point out that the problems such as academic under achievement, behavioral problems, and deficits in higher-order neurocognitive functions of the majority of nondisabled survivors persist throughout childhood and young adulthood [3], [4], [5]. Preventing preterm delivery, therefore, has been one of the impending problems in obstetrics practice.

Intrauterine infection, defined as chorioamnionitis (CAM) and funisitis, has been recently identified as a major cause of preterm delivery and the inflammatory response syndrome of the infants has been proven to be mediated by cytokines [6], [7]. A recent report has also revealed that CAM is a risk factor for both cerebral palsy (CP) and cystic periventricular leukomalacia of the infants [8]. However, CAM and funisitis are most often clinically silent and the histological examination of the placenta after delivery is the gold standard for their diagnosis [9]. It is also recognized that the relation between infection and preterm delivery is not consistent throughout gestation. That is, infection is present in most cases with early preterm deliveries before 30 weeks of gestation as shown by histologic examinations, and is rare in late preterm deliveries after 34 weeks [10]. It is therefore mandatory to establish treatment strategies for intrauterine infection in early gestational age.

On the other hand, it is revealed that antenatal diagnosis of fetal growth restriction (FGR) is associated with an increased risk of CP [11], and absent or reversed end-diastolic flow velocity (AREDFV) in the umbilical artery (UA) is an independent predictor of either neonatal decease or CP in preterm FGR infants [12]. FGR is a multifaceted condition which results in the birth of a small for gestational age (SGA) infant. It is also pointed out that being born SGA is associated with lower intelligence, poor academic performance, low social competence and behavioral problems [13], [14], [15], and some studies have indicated that children born SGA have long-term global cognitive impairment [16], [17], [18]. Although underlying mechanisms for FGR are heterogeneous, the most common cause is utero-placental dysfunction [19]. Fetal health during FGR may be determined from changes in regional fetal growth, behavior, cardiotocography and from studies of umbilical and regional fetal flow velocities using Doppler ultrasound. Because these changes may be related to the severity of the perinatal morbidity, the policy of delivery may be essential for short and long-term outcomes. In other words, if infants are delivered after fetal conditions have deteriorated with poor heart rate variability, they may be complicated by general issues relating to fetal hypoxia superimposed on prematurity that may worsen both of short and long-term outcomes. In contrast, early preterm delivery before fetal health deteriorates may increase the risk of complications due to prematurity [20]. In such a dilemma and under quite limited knowledge of long-term prognosis estimation, we obstetricians have been deciding when to deliver FGR infants with no established idea of what is the best prenatal management plan for short and long-term consequences of those premature infants.

Therefore, the purpose of the present study should be targeted to clarify the relationship between prenatal risk factors and neurodevelopmental outcomes of VLBW and extremely low birth weight (ELBW) infants.

Section snippets

Participants

This retrospective study investigated cases of Japanese women cared for through their pregnancy and delivery in our hospital during the period between October 2000 and December 2007. One hundred seventy women with a singleton pregnancy and their infants whose birth weight being less than 1500 g were included in this study. This study was approved by the Ethics Committee of Nagano Children's Hospital. We classified those infants into two groups, that is, 118 appropriate for gestational age (AGA)

Results

Table 1 shows the characteristics of the study population. Gestational age at delivery of the AGA group was significantly earlier than that of the SGA group (P < 0.001). Mortality (7.6% vs 15.4%, P = 0.12) and rate of infants who could not be evaluated by KSPD because of severe impairment (2.5% vs 1.9%, P = 0.806) were not significantly different between the two groups.

Table 2 shows the characteristics of the study population born between 25 and 31 gestational weeks. The gestational age at delivery

Discussion

According to the website of the Vital Statistics in Japan (http://www.mhlw.go.jp/toukei/saikin/hw/jinkou/kakutei04/) and the World Health Statistics of WHO (http://www.who.int/whosis/whostat/2009/en/index.html), mortality rates of neonates and infants in Japan in 2004 were 1.5 and 2.8 per 1000 live births, respectively and those are among the lowest figures in the world. And those of Nagano Prefecture where our hospital is located were 1.2 and 2.1, respectively. Moreover, according to the

Conflict of interest

The authors do not have any conflict of interest to disclose.

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Neurodevelopmental outcomes of very low birth weight and extremely low birth weight infants at 18 months of corrected age associated with prenatal risk factors

Abstract

Background

Aim

Study design

Subjects

Outcome measures

Results

Conclusion

Introduction

Section snippets

Participants

Results

Discussion

Conflict of interest

Lancet

Am J Obstet Gynecol

Early Hum Dev

J Am Acad Child Adolesc Psychiatry

Brain Res

Early Hum Dev

Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996–1997

Pediatrics

Neurologic and developmental disability at six years of age after extremely preterm birth

N Engl J Med

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

Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years

Pediatrics

Sequelae of chorioamnionitis

Curr Opin Infect Dis

Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis

JAMA

Intrauterine infection and preterm delivery

N Engl J Med

Maternal antecedents for cerebral palsy in extremely preterm babies: a case–control study

Dev Med Child Neurol

Prognostic value of umbilical artery Doppler studies in unselected preterm deliveries

Obstet Gynecol

The behavioral and emotional well-being of school-age children with different birth weights

Pediatrics