Cognitive impairment is independently related to low birth weight, low birth length and small head circumference. SGA children who have not experienced height and / or head circumference catch-up have the worst cognitive function. The serum IGF-1 level of short SGA children is significantly lower than that of catch-up SGA children. This may be due to the defect of GH-IGF-1 axis, resulting in some hGH / IGF-1 deficiency.

GH treatment can induce catch-up growth of head circumference, especially for those with small birth head circumference, growth hormone can help to improve IQ, behavior and self cognition of children with SGA.

Two years after birth is the most critical period for children's physical, neurological, cognitive and emotional development. This study evaluated the effect of growth hormone treatment on the improvement of cognitive function and growth and development of symmetrical SGA children who did not show catch-up growth from 6 months to 2 years old.

This is an innovative study. The minimum age of previous similar studies is 19 months. The starting age of this study is 6 months, and the results are to improve the cognitive development of SGA infants. This is the first of its kind. Although the safety of growth hormone in SGA infants younger than 2 years old has not been reported, it is based on a number of studies on the application of growth hormone in infants, such as PWS and GHD, It can be expected that there will be no short-term and long-term adverse reactions.

The study was conducted in 17 hospitals led by Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology

Subjects: SGA children from 6 months to 2 years old who meet the enrollment conditions shall be informed of the enrollment by the researcher and the subject's guardian, and the subject's guardian shall decide to participate in the test drug group or the control group.

GH treatment group (n = 68): the subjects were given PEG-rhGH injection 0.2 mg / kg / week (initial dose), once a week, subcutaneously before going to bed for 104 weeks. Each follow-up, the researchers adjusted the dosage according to the IGF-1 results of the center and other individual conditions.

Control group (n = 68): no treatment, only follow-up examination and growth and development related evaluation, and the follow-up time was 104 Week.

Inclusion Criteria:

1. Provide informed consent signed and dated by the subject's legal guardian;
2. The subjects met the clinical diagnosis of small for gestational age infants.
3. The age ranged from 6 months to 2 years old (including 6 months and 2 years old);
4. Height and head circumference are lower than the reference value - 2sd (including-2sd), whose weight is lower than the 10th percentile of the reference value of normal children of the same age and sex;
5. The total developmental quotient GQ calculated according to Griffiths mental development scale is less than 100 points (100 points) Indicates that the developmental age is consistent with the physiological age);
6. Birth gestational age ≥ 37 weeks and < 42 weeks, single birth and non test tube baby;
7. Symmetrical SGA: birth weight index > 2.0 (gestational age = 37 weeks), or > 2.2 (gestational age > 37 weeks) . Weight index [birth weight (g) × 100 / birth length (CM) ];
8. Normal thyroid function or normal after replacement therapy;
9. No previous rhGH treatment

Exclusion Criteria:

1. Patients with abnormal liver and kidney function (ALT > 2 times the upper limit of normal value, Cr > the upper limit of normal value);
2. Severe familial dwarfism (father height < 155cm or mother height < 145cm);
3. Definite neurological defects and / or severe neurodevelopmental retardation (the total development quotient calculated according to Griffiths mental development scale is less than 70), definite syndrome affecting cognitive development; Severe perinatal complications (such as severe asphyxia, sepsis, necrotizing enterocolitis, respiratory distress syndrome with long-term sequelae);
4. Genetic metabolic diseases (such as congenital hypothyroidism, phenylketonuria, methylmalonic acidemia);
5. Congenital skeletal dysplasia, or moderate or above scoliosis (or scoliosis ≥ 15 °) requiring treatment or claudication;
6. Short stature with other definite causes, such as osteochondral dysplasia and Turner syndrome (TS), Noonan syndrome (NS), Prader Willi syndrome (PWS), Angelman syndrome (as), silver Russell syndrome (SRS), or other genetically confirmed syndromes (Note: diseases that meet the clinical diagnostic criteria adopt the method of clinical diagnosis; when the clinical diagnosis is difficult to be clear, or the diagnosis of the disease depends on gene screening, the method of gene diagnosis shall be supplemented / adopted);
7. patients with diabetes or fasting blood glucose are abnormal and the researchers believe that they may affect the safety of subjects.
8. Continuous application of other hormone therapy or systemic glucocorticoid therapy for more than one month in the past 6 months (local or inhaled glucocorticoids are allowed);
9. Patients with a history of convulsions or epilepsy, except for the relief or recovery of convulsions or epilepsy symptoms after the release of definite causes (such as high fever, calcium deficiency, brain infection, etc.);
10. Patients with other systemic chronic diseases;
11. Patients with confirmed tumors, or patients with family history of tumors (two or more tumor patients within three generations of immediate relatives), previous tumor history or considered as patients with high risk of tumors in combination with other information, clear syndromes with high risk of tumors (such as Bloom syndrome, Fanconi syndrome, Down syndrome, etc.);
12. Known high allergic constitution or allergic to the test drug in this study;
13. Those who have participated in clinical trials of other drugs within 3 months (the placebo group is not subject to this restriction);
14. Have received drug treatment that may interfere with GH secretion or GH effect within 3 months (including but not limited to any type of recombinant human growth hormone and protein assimilation drugs (including but not limited to oxandron, danazol and stanazol) other than rhGH injection);
15. The investigator considers that it is not suitable to be selected for this clinical trial.