This observational study was conducted from Janauary 2014 to Janauary 2015 in a tertiary-care neonatal unit at Kalawati Saran Children’s Hospital, Lady Hardinge Medical College, New Delhi, India. The study was approved by the Institutional ethics committee, and informed consent was taken from each parent before inclusion in the study.

Demographic data, maternal history, labor details and neonatal details were recorded in a tested proforma. Admitted neonates were managed as per standard treatment protocol of the department. The parents of all the enrolled neonates were instructed to report for follow up at 40 weeks PMA of the baby. The parents were reminded telephonically two days before and on the day of follow-up.

NAPI is a standardized kit of neonatal neurobehavioral status [7] which measures the progression of the neurobehavioral performance and can be used effectively to screen preterm infants, monitor their individual progress and assess the effects of NICU interventions. NAPI is appropriate for infants between 32 weeks post conceptional age (PCA) and term.

At 40 weeks PMA, each baby underwent an assessment for the neurobehavioral status according to the NAPI score. Scoring was done on the record forms provided with the standard NAPI kit. The examination was carried out in the nursery/neonatal ward, 45 minutes prior to next feeding time. The infant to be examined was placed under a radiant warmer with temperature probes attached. At the beginning of the examination, the behavioral state was observed and recorded according to the categories stated in the record form provided. The NAPI items were administered in an invariant sequence and assessment was done for two clusters, Motor Development-Vigor and Alertness-Orientation. Subse-quently raw scores were transposed into percentage scores to ensure comparability between items, combined and averaged into clusters. For all participants, NAPI was administered by one investigator who was blinded about the group allotment.

Primary outcome variable was Neurobehavioral score by NAPI at 40 weeks of PMA for MDV (Motor development- vigor) and AO (Alertness-orientation). Neonates identified as neurobehaviorally deviant were referred for early stimulation and developmental rehabilitation.

For a power of 80% with an alpha error of 0.05 and an assumed difference of 20% between the groups, the total sample size estimated was 48 (24 in each limb). Assuming a lost to follow-up/dropout rate of 10-15% and rounding off, a total of 60 preterm neonates were enrolled.

Statistical analysis: The quantitative variables were compared using Mann-Whitney test. The qualitative variables were compared using Chi-square/Fisher’s exact test.　A P value of <0.05 was considered statistically significant.　 SPSS version 15.0 software was used for statistical analysis.　

The flow of participants into the study is presented in Fig.1. There was no significant difference between the two groups with respect to general demographic profile, antenatal findings and resuscitation details, except more males among controls (Table I).

Fig. 1 Study flow diagram.

TABLE I	Comparison of Baseline Characteristics of Neonates Born to Mothers with Pre-eclampsia and Controls 

The median NAPI score of MDV (Motor development- vigor) and AO (Alertness-orientation) in babies of pre-eclamptic mothers in cases were significantly lower as compared to the controls [60.8 (53.64-64.4) vs 66.4 (61.58-78.61); P <0.001for MDV] and [36.4 (27.76 - 45.25) vs 44.6 (35.25 - 56.89); P=0.006 for AO]. This indicates that neonates born to mothers with pre-eclampsia had less mature neurobehavior as compared to babies born to mothers without pre-eclampsia.

In the present study NAPI assessment was done at 40 weeks of post conceptional age. The mean NAPI score of MDV and AO was less in pre-eclampsia group as compared to controls which indicates that neonates born to mothers with pre-eclampsia had less mature neurobehavior.

NAPI has been evaluated as a tool to asses neurobehavior in preterm neonates including late preterm neonates has not shown any difference in SGA and AGA neonates [21]. There are no published studies in the literature, to the best of our knowledge, which have evaluated the neurobehavioral outcomes in late preterms born to pre-eclamptic mothers. It is thus postulated that pre-eclampsia independently affects the neurobehavioral maturity of preterm neonates.

A recent study by Salzbank, et al. [11] evaluated the effect of pre-eclampsia on neurobehavior of infants at 6 months postpartum. The neurobehavioral assessment in this study was done using Infant Behaviour Questionnaire-Revised at six months post-partum [11]. There are many other studies which have evaluated neurodevelopmental outcomes in neonates born to pre eclamptic mothers at later age. Previous authors [12,13] have shown that neonates born to pre-eclamptic mothers had lower MDI (Mental Development Index) scores at 24 months of age and lower mean PPVT-R (Peabody picture vocabulary test) scores.

There is also a positive correlation between NAPI and scales of neurodevelopment done at later age. Studies have shown positive correlation between NAPI and BSID at 18 months [14,15]. Other studies [16] suggest that early or short term neurobehavioral assessment is a useful tool for early identification and rehabilitation of infants at risk for a poor outcome [16].

The major limitation of the study is that the role of pre-eclampsia on neurodevelopment was not assessed in very and extreme preterm neonates, who are more likely to be susceptible to disabilities. The importance of the study lies in the fact that babies with poor neurobehavior can be detected early and appropriate intervention measures can be undertaken. The follow-up of study subjects was only conducted till 40 weeks and a longer follow up for deviant neurodevelopmental outcomes would have been prudent at 12 and 18 months of chronological age using structured neurodevelopment assessment tools.

This study raises the possibility of poor neurobehavioral outcomes in late preterm neonates born to mothers with pre-eclampsia, and the possibility of early identification, thereby assisting in interventions and close follow-up.

Contributors: PB: designed study, enrolled study participants, conducted follow up, prepared manuscript; VD: designed study, approved manuscript, gave critical inputs throughout the study period; AS: gave critical inputs, reviewed manuscript.

Funding: None; Competing Interest: None stated.

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