Objective: To investigate the effects of enriched environments on behavioral development at toddler period of preterm who had experienced early repeated operative pain. Methods: A cross-sectional study was conducted. A total of 80 high-risk preterm children of 2 years of age, who had experienced repeated pain stimuli in the neonatal intensive care unit (NICU), were enrolled as preterm group from the High-risk Children Clinic of Children\'s Hospital of Nanjing Medical University from October 2016 to March 2021. Furthermore, 39 full-term healthy children, aged 2 years, who were undergoing routine check-ups during the same period, were selected as the full-term group. The preterm group was further divided into preterm intervention group and preterm non-intervention group based on the implementation of enriched environment interventions. Data of neonatal characteristics from 3 groups were collected. Growth and development indicators at the age of 2 years were measured. Neuropsychological development evaluated by Gesell developmental scale. Behavioral development evaluated by child behavior check list. The salivary cortisol levels in response to novelty (baseline, task, end) were collected. The family environment, including maternal parenting pressure, were evaluated through a survey questionnaire. One-way ANOVA and least significant difference (LSD) tests were used to compare physical development, maternal parenting stress, Gesell neuropsychological development, and behavioral problems among the 3 groups. A repeated-ANOVA and LSD tests were employed to compare the patterns of salivary cortisol secretion. Pearson correlation analysis was used to explore the influencing factors related to neuropsychological and behavioral development and cortisol level. Results: There were 44 cases in the preterm intervention group (17 males, gestational age of (31.3±2.8) weeks), and 36 in the preterm non-intervention group (29 males, gestational age of (32.5±2.6) weeks). The full-term group consisted of 39 children (23 males, gestational age of (39.3±2.1) weeks). At 2 years of age, the height, weight, and head circumference of the preterm intervention group and non-intervention group were all lower than those of the full-term group (all P<0.05).The Gesell developmental schedule showed that the preterm non-intervention group scored all lower in gross motor, fine motor, adaptive, language and personal-social domains compared to the full-term group (91±7 vs. 97±6, 88±9 vs. 94±6, 89±8 vs. 99±8, 84±10 vs. 100±15, 89±7 vs. 95±6), with statistical significance (all P<0.01). The preterm intervention group scored all higher than the preterm non-intervention group in gross motor, fine motor, adaptive and language domains (all P<0.05), with no significant difference compared to the full-term group (all P>0.05). The number of needle painful procedures during hospitalization in NICU of the non-intervention group was negatively correlated to the adaptive development quotient (r=-0.48, P<0.05). Furthermore, the preterm non-intervention group exhibited higher scores in social withdrawal, depression, somatic complaints, aggression, and destructive behaviors compare to the full-term group and preterm intervention group (F=8.07, 5.67, 7.72, 7.90, 7.06; all P<0.05); while the preterm intervention group showed no significant difference compared to full-term group (all P>0.05). Behavioral problems (social withdrawal and depression) in the preterm non-intervention group were positively correlated with maternal parenting stress (r=0.66, 0.50; both P<0.05). In response to novel visual stimuli and cognitive challenges, the preterm non-intervention group had significantly higher salivary cortisol levels compared to the full-term group (P=0.006), which were negatively correlated with the frequency of early painful procedures (r=-0.83, -0.80; both P<0.01). There was no significant difference in cortisol secretion pattern between the intervention group and the full-term group (P=0.772). Conclusion: Enriched environmental interventions can improve neuropsychological development, decrease behavioral problems, and down-regulate consistent high cortisol response to task in preterm infants who have experienced repeated procedural pain in the NICU by the age of 2 years.
目的: 探讨丰富环境对早期经历反复操作性疼痛早产儿幼儿期行为发育的影响。 方法: 横断面研究,纳入2016年10月至2021年3月在南京医科大学附属儿童医院高危儿门诊建档并随访至2岁的80例高危早产儿(既往在新生儿重症监护病房经历反复疼痛刺激),作为早产儿组;选取同期本院儿童保健科门诊体检的39名足月出生的2岁健康儿童,作为足月儿组。早产儿组根据丰富环境具体实施情况,分为早产儿干预组和早产儿对照组。收集3组儿童出生资料,测量2岁时生长发育指标,Gesell发育量表评估神经心理发育,儿童行为量表评估行为发育情况,收集唾液检测面对新奇事物不同时间点(基线、任务态、结束时)皮质醇水平,通过调查问卷评估家庭环境包括母亲育儿压力等。采用单因素方差分析和最小显著差异法(LSD)检验比较3组儿童体格发育情况、母亲育儿压力、神经心理发育和行为问题;重复方差分析和LSD检验比较3组唾液皮质醇的分泌变化;运用Pearson相关分析法分析儿童神经心理以及行为发育和皮质醇分泌的相关影响因素。 结果: 早产儿干预组44例,其中男17例,出生胎龄(31.3±2.8)周;早产儿对照组36例,其中男29例,出生胎龄(32.5±2.6)周;足月儿组39名,其中男23名,出生胎龄(39.3±2.1)周。早产儿干预组和早产儿对照组在2岁时的身长、体重和头围均低于足月儿组(均P<0.05)。早产儿对照组儿童Gesell发育量表评估大动作、精细动作、适应性、语言和个人社交的发育商均低于足月儿组(91±7比97±6,88±9比94±6,89±8比99±8,84±10比100±15,89±7比95±6,均P<0.01);早产儿干预组在大动作、精细动作、适应性和语言方面发育商均高于早产儿对照组(均P<0.05),与足月儿组差异均无统计学意义(均P>0.05)。早产儿对照组的新生儿重症监护病房经历针刺性操作次数与2岁时适应性发育商呈负相关(r=-0.48,P<0.05)。早产儿对照组儿童社交退缩、抑郁、躯体不适、攻击行为及破坏性行为得分均高于足月儿组和早产儿干预组(F=8.07、5.67、7.72、7.90、7.06,均P<0.05);早产儿干预组与足月儿组差异均无统计学意义(均P>0.05)。早产儿对照组的行为问题(社交退缩、抑郁)均与母亲育儿压力呈正相关(r=0.66、0.50,均P<0.05)。在面对视觉新奇事物时,早产儿对照组唾液皮质醇随任务时间变化分泌水平持续高于足月儿组(P=0.006),与早产儿在新生儿重症监护病房经历的致痛性操作次数以及针刺性疼痛次数均呈负相关(r=-0.83、-0.80,均P<0.01)。早产儿干预组皮质醇随时间变化趋势与足月儿组差异无统计学意义(P=0.772)。 结论: 丰富环境干预可改善在新生儿重症监护病房经历反复操作性疼痛的早产儿2岁时神经心理发育,纠正不良行为问题,下调任务态时皮质醇的高分泌水平。.