Prevalence and Risk Factors of Developmental Delay among High-risk Preterm NICU Graduates – A Cross-Sectional Study

INTRODUCTION

Preterm refers to live births before 37 completed weeks of gestation and is categorized as extreme preterm (<28 weeks), very preterm (28 to <32 weeks), and moderate-to-late preterm (32–37 weeks) based on the gestational age. An estimated 13.4 million babies were born before completing 37 weeks of gestation in the year 2020.^[1] The rates of preterm births vary in different countries and range from 4% to 16%. Complications related to preterm birth are a leading cause of death among children under 5 years of age and were responsible for approximately 90000 deaths in the year 2019. The survival rates also vary with countries, and only half of the babies born at or <32 weeks gestation in low-income countries survive in contrast to high-income countries where almost all babies in this category survive.^[2]

India is a major contributor to global preterm birth, with nearly one in six live births being preterm. However, the prevalence of preterm birth is unevenly distributed within states of India, ranging from 9% to 16%.^[3] Studies from low and middle-income countries have reported that preterm births are at higher risk for neonatal mortality compared with full-term births.^[3] Similar observations have been made in some Indian studies. Among those preterm babies who survive, disabilities such as hearing deficit, visual problems, and learning disabilities are common.^[2,4,5]

Preterm and low birth weight neonates have better survival with advances in neonatal care. However, they are vulnerable to developing neurodevelopmental handicaps more frequently compared to their term counterparts.^[6] Studies have shown that gestational age, birth weight, need for cardiopulmonary resuscitation at birth, mechanical ventilation, neonatal morbidities like bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, and duration of hospital stay were the common factors that influenced the neurodevelopmental outcome of neonatal intensive care unit (NICU) graduates.^[7]

Although the risk of significant neurodevelopmental delay is high in extreme prematurity, it has been observed that moderate to late preterm neonates who require NICU care are also at risk.^[8] Preterm neonates have differences in neurological status, intellectual functioning, school performance, and behavior when compared to term neonates. Although severe handicaps can be picked up by 2 years of age, longer follow-up can identify subtle changes in behavior, motor coordination, visual motor integration, and perception.^[9] The study objective was to determine the prevalence of developmental delay in high-risk preterm NICU graduates and to determine the risk factors for developmental delay in them.

MATERIAL AND METHODS

This study was an analytical cross-sectional study conducted in the department of pediatrics of a tertiary care medical college hospital from October 2021 to October 2022. The study was commenced after obtaining approval from the Institutional ethics committee (Study ID 609/2021, meeting held on October 07, 2021). Infants born as high-risk preterm neonates who required NICU stay in the early neonatal period were included in the study at a corrected age of 1 year. The study participants were all infants who were born as preterm neonates and who required NICU stay in the early neonatal period. All preterm neonates with gestational age <37 weeks and any birth weight category who survived till 1 year of age were included. The birth weight of the neonates was recorded from the documents. The discharged neonates were followed up in the high-risk newborn out patient (OP) from where the infants were enrolled into the study at a corrected age of 1 year.

Infants whose parents did not consent to the study were excluded from the study. The sample size was calculated from a previous study, which reported a 24% prevalence of neurodevelopmental delay among preterm at 1-year follow-up with an error margin of 8% to calculate a 95% confidence interval (CI), and the sample size was calculated to be 110.^[10]

The infants were included in the study after obtaining informed parental consent. Details of maternal, perinatal, and neonatal risk factors were noted from the child’s NICU discharge summary in a structured pro forma. All the admitted preterm neonates undergo an ultrasonogram cranium as a routine in the NICU both during the stay and also before discharge. The details of the sonogram were available in the discharge summary.

All infants included in the study were part of the follow-up program in the high-risk newborn follow-up clinic and were assessed for growth and development periodically. A detailed neurological examination was done. During the follow-up of high-risk neonates, clinical assessment tools like AmielTison angles were used. Details regarding the passive tone and active tone were documented in the follow-up card and reviewed.

Developmental screening was done using the Trivandrum developmental screening test. Only TDSC was used in screening, and confirmatory tests were not used in the study center. Although TDSC is not a confirmatory test, in a resource-limited setting, it may help to identify infants with delays in development early and refer them to a higher center.

RESULTS

The present study included infants who were high-risk preterm NICU graduates, of whom 57.2% were males and 42.8% were females. 22.7% of infants had birth weight <1750 g, while 77.3% weighed more than 1750 g at birth. All preterm neonates who were included in the study were also part of the retinopathy of prematurity screening program, which is an ongoing program till the age of 1 year. As the birth weight cut-off used in retinopathy of prematurity (ROP) screening is 1750 g, the same cut-off was used to study the risk of developmental delay.

The prevalence (95% CI) of developmental delay was 18% (12.2–27.6% [Table 1]). There are, 18% of infants with gross motor delay, 13% with delay in fine motor development, 18% with delayed language development, and 14% with delay in social and adaptive milestones. Among the 20 infants with developmental delay, there were 13 infants with global developmental delay, motor and language delay in 1 infant, language and social delay in 2 infants, isolated language delay in 1 infant, and isolated motor delay in 3 infants.

Among the maternal and perinatal risk factors, it was observed that gestational diabetes was present in 25.4%, pregnancy-induced hypertension in 28.1%, antepartum hemorrhage in 2.7%, multiple gestation in 15.4%, and lower segment cesarean section (LSCS) in 48% of neonates. The prevalence of developmental delay was lower among neonates of mothers with gestational diabetes (14.3% vs. 19.5%) [Table 2].

The prevalence of developmental delay was higher among neonates of mothers with risk factors such as pregnancy-induced hypertension (22.6% vs. 16.5%), antepartum hemorrhage (33% vs. 17.8%), and multiple gestation (29.4% vs. 16.1%). Among the neonatal risk factors, 10% had apnea, 58% had respiratory distress syndrome, 25.4% had sepsis, 1% had an intraventricular hemorrhage, 65.4% were administered oxygen, and 7.2% were given blood transfusion. No formal illness severity scores were used in the study population. However, many of the variables usually used in severity scores were periodically assessed during the stay in the NICU. The prevalence of developmental delay was higher among neonates with birth weight <1.75 kg (48% vs. 9.4%), gestational age between 28 and 32 weeks (36.8% vs. 8.3%), who had apnea (63.6% vs. 13.1%), respiratory distress syndrome (RDS) (31% vs. 3.8%), and sepsis (39.3% vs. 11%) [Table 3].

The bivariate analysis identified birth weight <1.75 kg, gestational age of 28–32 weeks, neonatal morbidities such as apnea, respiratory distress syndrome, and sepsis, and interventions such as oxygen therapy and blood transfusion as risk factors for developmental delay, which is shown in Table 4. Multivariate logistic regression revealed birth weight <1.75 kg in the neonatal period to be an independent risk factor, which is depicted in Table 5.

DISCUSSION

The present study was conducted on infants who were admitted to our NICU; the NICU is a 40 bedded unit with 3195 admissions during the study period. It is a predominantly intramural unit, with the majority of the neonates being delivered in the hospital. During the study period, there were 137 deaths, which amounted to a death rate of 4.3%. The present study revealed a prevalence of developmental delay of 18% among the high-risk preterm NICU graduates. Assessment of these infants showed that motor delay was more common than delay in social and adaptive development. Language delay was the least common morbidity encountered. Delays in language and social milestones were considered if the infant did not develop the age-appropriate milestones in these domains. As the study was done at the corrected age of 12 months, the delay in language and social milestones was considered if the infants had not developed the early milestones in the language and social domains.

Apnea in the neonatal period and birth weight <1.75 kg were significant risk factors for developmental delay.

Similar studies done earlier have arrived at varying prevalences of developmental delay among preterm NICU graduates, ranging from 14.6% to 50.4%.^[6,11] Variation in the prevalence may be due to differences in the gestational age and morbidity pattern at the time of admission to the NICU. In countries with high neonatal mortality, a study done on preterm <32 weeks had identified a pooled estimate of 24.6% (95% CI: 15.3–33.9%) for moderate-to-severe impairment, while for mild impairment, it was 32.4% (95% CI: 15.4–49.4%).^[12] Compared to earlier studies, it was observed in the present study that there was a relatively lower prevalence of developmental delay. This was probably due to higher mortality among extremely low birth weight (ELBW) and very low birth weight (VLBW) neonates in the unit as well as developmentally supportive practices in the unit. developmentally supportive care (DSC) was a routine practice done on all neonates admitted to the NICU. As the rates of developmental delay were lower in this study, it was postulated to be due to the regular practice employed in the NICU. However, the role of DSC was not evaluated in the study.

A study comparing the neurodevelopmental outcome of late preterm and early term babies identified predominantly gross motor delay in late preterm and fine motor delay in term neonates.^[13] This was similar to our observations of predominant gross motor delay in the preterm neonates. Higher gestational age at birth and higher birth weight were associated with a lower risk of developmental delay.^[14]

Neurodevelopmental delay is multifactorial and is likely a consequence of an immature brain, perinatal risk factors, and environmental exposures. In the present study, it was observed that apnea was a significant independent risk factor for developmental delay. Previous studies have observed that the number of days apnea had occurred correlated positively with neurodevelopmental impairment and increasing apnea days was found to be associated with poor neurodevelopmental outcome.^[15] Delayed resolution of apnea and higher daily apnea were associated with poorer neurodevelopmental outcomes evaluated at 13 months.^[16] Apnea and the associated desaturation and hypoxia are said to be the factors influencing the neurological outcome of preterm babies. However, the extent to which apnea is causative of this neurodevelopmental delay or is just associated with a background of other sequelae of prematurity remains unclear.^[17]

Delay, preterm/low birth weight babies were more likely to have developmental delay compared to their term counterparts. Intellectual disability and neurodevelopmental deficits are more common in this population. Low birth weight babies have delays in gross motor, cognitive, and communication skills. Very low birth weight neonates are at high risk of developmental difficulties and poor cognitive and motor outcomes. It has been observed that even apparently normal, very low birth weight children had a greater risk of delay in development when compared to those with normal birth weight. The greatest risk of delay in development was among preterm, very low birth weight babies who were appropriate for gestational age.

CONCLUSION

18% of high-risk preterm NICU graduates had neurodevelopmental delay at 1 year of age, and apnea and birth weight <1.75 kg were significant independent risk factors for developmental delay in this population. Developmentally supportive newborn care should be given to all high-risk newborns during NICU stay, and all high-risk NICU graduates should receive periodic follow-up and early intervention to achieve optimal development.