Summary of Infants Weighing 500 Grams or Less

Study Overview
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Brief Summary
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This is a retrospective single-center cohort study. The comparison in short- and long-term outcomes will be made between those with and without primary microcephaly in infants weighing ≤ 500 g.

Detailed Description
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This is a retrospective single-center cohort study. The study setting is a level IV neonatal intensive care unit (NICU) at Nagano Children's Hospital in Nagano, Japan. We will retrospectively collect the data of those who were admitted to Nagano Children's Hospital NICU between January 1, 2015, and December 31, 2019. Eligible infants will be identified using our neonatal database and clinical records. The extracted data includes maternal background information and clinical course, infant's status at birth, the clinical course in NICU, and the follow-up data at 6 and 18 months of corrected age. Among the eligible infants, those with a z score of birth head circumference < -2 will be classified into the Microcephaly group and others into the Control group. The z score is calculated using the Japanese growth standard.

Official Title
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Microcephaly at Birth as a Potential Predictor of Poor Prognosis in Infants Weighing 500 Grams or Less: a Retrospective Cohort Study

Conditions
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Infant, Extremely Low Birth Weight, Microcephaly

Intervention / Treatment
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* Diagnostic Test: Microcephaly


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Live-born infants weighing ≤ 500 g at birth Infants whose clinical course is available in the electronic medical record Exclusion Criteria: Stillbirths Infants who received only palliative care at birth Outborn infants Infants whose assessment at 3 years of age not completed at data analysis
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Microcephaly<br>Infants with primary microcephaly. | Diagnostic Test: Microcephaly<br>* Those with a z score of birth head circumference < -2 (primary microcephaly) are classified into the Microcephaly group.<br>|
| Control<br>Infants without primary microcephaly. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of neurodevelopmental impairment | Having at least one of the following conditions: cognitive impairment, cerebral palsy, visual impairment, or hearing impairment. Cognitive impairment was defined as a modified DQ score of ≤ 70 using the Kyoto Scale of Psychological Development. CP was defined as (1) a non-progressive disorder of the central nervous system appearing in the early years of life and clinically characterized by a persistent but not unchanging impairment of movement and posture and/or (2) the Gross Motor Function Classification System level ≥ II. Visual impairment was defined as unilateral or bilateral blindness, or any other condition requiring corrective lenses, which were diagnosed or determined by ophthalmologists. Hearing impairment was defined as unilateral or bilateral hearing loss that requires a hearing aid. The diagnosis of hearing loss was made by otolaryngologists using auditory steady-state response. | 3 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate | Survival rate is the proportion of those have survived. | At discharge from neonatal intensive care unit, an average at 40 weeks' postmenstrual age. | 
| Rate of severe bronchopulmonary dysplasia | The definition of bronchopulmonary dysplasia proposed by the National Institute of Child Health and Human Development is used to classify the severity of bronchopulmonary dysplasia. Those who need ≥ 30% of oxygen or any mechanical respiratory support at 36 weeks of gestation are classified as having severe bronchopulmonary dysplasia. | At 36 weeks' postmenstrual age | 
| Rate of need for surgery for patent ductus arteriosus | Patent ductus arteriosus is diagnosed by neonatologists using echocardiography and clinical signs. | In neonatal intensive care unit, an average of up to 4 weeks of life | 
| Rate of severe intraventricular hemorrhage | Intraventricular hemorrhage is diagnosed by neonatologists using head ultrasound. Severe IVH was defined as grade III or IV by the classification of Papile. | In neonatal intensive care unit, an average of up to 2 weeks of life | 
| Rate of periventricular leukomalacia | Periventricular leukomalacia is diagnosed using head ultrasound or magnetic resonance imaging, typically cysts formation in the periventricular white matter. | In neonatal intensive care unit, an average of up to 40 weeks' postmenstrual age | 
| Rate of necrotizing enterocolitis | The diagnosis with necrotizing enterocolitis. | In neonatal intensive care unit, an average of up to 2 weeks of life | 
| Rate of sepsis | Sepsis is defined as septicemia or bacteremia with a positive culture result of the blood and/or cerebrospinal fluid. | In neonatal intensive care unit, an average of up to 4 weeks of life | 
| Rate of need for treatment for retinopathy of prematurity | The diagnosis of retinopathy of prematurity and the decision on the need for treatment were made by ophthalmologic examination. | In neonatal intensive care unit, an average of up to 40 weeks' postmenstrual age | 
| Weight | Physical measurement. | At 40 weeks' postmenstrual age or at discharge (approximately 40 weeks' postmenstrual age) | 
| Length | Physical measurement. | At 40 weeks' postmenstrual age or at discharge (approximately 40 weeks' postmenstrual age) | 
| Head circumference | Physical measurement. | At 40 weeks' postmenstrual age or at discharge (approximately 40 weeks' postmenstrual age) | 
| Postmenstrual age | Postmenstrual age is calculated based on their gestational age and date at birth. | At discharge, an average at 40 weeks' postmenstrual age | 
| Need for home oxygen therapy | Need for home oxygen therapy. | At discharge, an average at 40 weeks' postmenstrual age | 
| Tracheostomy | Need for tracheostomy. | In neonatal intensive care unit, an average at 40 weeks' postmenstrual age | 
| Length of hospital stay | The initial hospitalization. | In neonatal intensive care unit, an average at 40 weeks' postmenstrual age | 
| Survival rate | Survival rate is the proportion of those have survived. | At 3 years of age | 
| Modified developmental quotient | Modified developmental quotient is calculated by dividing developmental age (measured by the Kyoto Scale of Psychological Development) by the corrected age. | At 3 years of age | 
| Rate of cerebral palsy | Cerebral palsy is defined as (1) a non-progressive disorder of the central nervous system appearing in early years of life and clinically characterized by a persistent but not unchanging impairment of movement and posture and/or (2) the Gross Motor Function Classification System level ≥ II. | At 3 years of age | 
| Rate of visual impairment | Visual impairment is defined as unilateral or bilateral blindness, or any other condition requiring corrective lenses, which were diagnosed or determined by ophthalmologists. | At 3 years of age | 
| Rate of hearing impairment | Hearing impairment is defined as unilateral or bilateral hearing loss that requires a hearing aid. The diagnosis of hearing loss was made by otolaryngologists using auditory steady-state response. | At 3 years of age | 
| Rate of those who need home oxygen therapy | Need for home oxygen therapy. | At 3 years of age | 
| Rate of those who need tracheostomy | Need for tracheostomy. | At 3 years of age | 
| Rate of those who need tube feeding or gastrostomy | Need for tube feeding or gastrostomy. | At 3 years of age | 
| Rate of those who need rehospitalization | Need for rehospitalization. | After 18 months of corrected age unit until 3 years of age | 
| Weight | Physical measurement. | At 3 years of age | 
| Height | Physical measurement. | At 3 years of age | 
| Head circumference | Physical measurement. | At 3 years of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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500 grams or less, prognosis