BACKGROUND: The neurotoxicity of general anesthesia to the developing human brains is controversial. We assessed the associations between surgery under general anesthesia in infancy and development at age 1 year using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: In the JECS, 103,062 pregnancies and 104,065 fetuses were enrolled between January 2011 and March 2014. Of the 100,144 registered live births, we excluded preterm or post-term infants, multiple births, and infants with chromosomal anomalies and/or anomalies of the head or brain. Data on surgical procedures under general anesthesia in infancy were collected from self-administered questionnaires by parents at the 1-year follow-up. Developmental delay at age 1 year was assessed using the Japanese translation of the Ages and Stages Questionnaires, Third Edition (J-ASQ-3), comprising five developmental domains. RESULTS: Among the 64,141 infants included, 746 infants had surgery under general anesthesia once, 90 twice, and 71 three or more times. The percentage of developmental delay in the five domains of the J-ASQ-3 significantly increased with the number of surgical procedures. After adjusting for potential confounding factors, the risk of developmental delays in all five domains was significantly increased in infants who had surgery under general anesthesia three times or more (adjusted odds ratios: for communication domain 3.32; gross motor domain 4.69; fine motor domain 2.99; problem solving domain 2.47; personal-social domain 2.55). CONCLUSIONS: Surgery under general anesthesia in infancy was associated with an increased likelihood of developmental delay in all five domains of the J-ASQ-3, especially the gross motor domain at age 1 year. The neurodevelopment with the growth should be further evaluated among the children who had surgery under general anesthesia. TRIAL REGISTRATION UMIN Clinical Trials Registry (number: UMIN000030786 ).
Anesthesia, General ; adverse effects ; Anesthetics, General ; adverse effects ; Child Development ; drug effects ; Cohort Studies ; Female ; Humans ; Infant ; Infant, Newborn ; Japan ; Male

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.
Body Height ; Body Mass Index ; Body Weight ; Child Development/drug effects* ; Cohort Studies ; Dietary Supplements ; Docosahexaenoic Acids/pharmacology* ; Female ; Humans ; Infant ; Infant, Newborn/physiology* ; Maternal-Fetal Exchange ; Parturition ; Pregnancy ; Pregnancy Outcome ; Prenatal Care ; Weight Gain

OBJECTIVEThe number of analyzed outcome variables is important in the statistical analysis and interpretation of research findings. This study investigated published papers in the field of environmental health studies. We aimed to examine whether differences in the number of reported outcome variables exist between papers with non-significant findings compared to those with significant findings. Articles on the maternal exposure to mercury and child development were used as examples.

METHODSArticles published between 1995 and 2013 focusing on the relationships between maternal exposure to mercury and child development were collected from Medline and Scopus.

RESULTSOf 87 extracted papers, 73 used statistical significance testing and 38 (43.7%) of these reported 'non-significant' (P>0.05) findings. The median number of child development outcome variables in papers reporting 'significant' (n=35) and 'non-significant' (n=38) results was 4 versus 7, respectively (Mann-Whitney test P-value=0.014). An elevated number of outcome variables was especially found in papers reporting non-significant associations between maternal mercury and outcomes when mercury was the only analyzed exposure variable.

CONCLUSIONAuthors often report analyzed health outcome variables based on their P-values rather than on stated primary research questions. Such a practice probably skews the research evidence.

Bias ; Child ; Child Development ; drug effects ; physiology ; Environmental Exposure ; statistics & numerical data ; Environmental Health ; statistics & numerical data ; Female ; Humans ; Maternal Exposure ; statistics & numerical data ; Mercury ; toxicity ; Outcome Assessment (Health Care) ; standards ; Periodicals as Topic ; standards ; statistics & numerical data

OBJECTIVETo study the analgesic effect and safety of fentanyl in neonates receiving mechanical ventilation.

METHODSThirty neonates receiving mechanical ventilation between December 2010 and February 2011 were randomized into drug intervention group and control group (n=15 each). In addition to the conventional treatment for both groups, the drug intervention group received fentanyl as the analgesic treatment. Heart rate, respiratory rate, blood pressure changes, and premature infant pain profile (PIPP) score before treatment and at 30 minutes, 2 hours, and 4 hours after treatment were recorded in both groups. Follow-up visits were performed for these infants after discharge, and the CDCC intellectual development scale for infants was applied to measure mental development index (MDI) and psychomotor development index (PDI) at 3, 6, 9, and 12 months of age.

RESULTSThe respiratory rate and heart rate decreased in the drug intervention group after fentanyl treatment compared with the control group (P<0.05), and the PIPP scores in the drug intervention group was significantly lower than in the control group (P<0.05). The results of follow-up visits showed no significant differences in MDI and PDI at 3, 6, 9 and 12 months of age between the drug intervention and control groups (P>0.05).

CONCLUSIONSFentanyl can relieve the pain response in neonates receiving mechanical ventilation, with no long-term adverse effects on neurodevelopment.

Analgesics, Opioid ; pharmacology ; Child Development ; drug effects ; Female ; Fentanyl ; pharmacology ; Heart Rate ; drug effects ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Respiration ; drug effects ; Respiration, Artificial

OBJECTIVETo evaluate the effect of neonatal perioperative anesthetic exposure in complex cardiac surgery on neurodevelopmental outcomes in preschool children.

METHODSGeneral clinical data and data concerning anesthetic exposure were collected from 89 infants undergoing complex cardiac surgery at Sichuan People' Hospital. The cohort was followed for neurodevelopment till preschool age (48-72 months) and assessed with Wechsler Preschool and Primary Scale of Intelligence-III, Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II.

RESULTSSeventy-one children were enrolled into the final analysis. Multiple linear regression found days on benzodiazepines (beta;=-0.49, P=0.005) and cumulative dose of benzodiazepines (β=-0.10, P=0.023) were associated with the full-scale IQ in these preschool children. Days on benzodiazepines (beta;=-0.39, P=0.009) and on chloral hydrate (beta;=-1.19, P=0.020) were associated with lower performance intelligence quotient (PIQ) at the preschool age. Cumulative dose of benzodiazepine exposure (beta;=-0.008, P=0.012) was associated with lower VMI scores. No correlations of other sedation/analgesia variables were found with the full-scale IQ, PIQ, Verbal IQ, VMI, or GAC scores.

CONCLUSIONWe found a significant association of days on benzodiazepines, cumulative dose of benzodiazepines, and days on chloral hydrate in neonatal cardiac surgery with neurodevelopmental outcomes at the preschool age, suggesting the need of minimizing anesthetic exposure during a neonatal cardiac surgery to improve the children's neurodevelopmental outcomes.

Anesthetics ; administration & dosage ; adverse effects ; Benzodiazepines ; administration & dosage ; adverse effects ; Cardiac Surgical Procedures ; Child ; Child Development ; drug effects ; Child, Preschool ; Chloral Hydrate ; administration & dosage ; adverse effects ; Humans ; Infant, Newborn ; Linear Models ; Multivariate Analysis ; Perioperative Period

OBJECTIVETo observe the efficacy of regular or intermittent inhalation of salmeterol/fluticasone propionate (SM/FP) in the treatment of bronchial asthma and its effects on growth and development in children.

METHODSA total of 112 children diagnosed with bronchial asthma between September 2012 and October 2013 were assigned to standardized treatment (standard group, n=56) and non-standardized treatment (intermittent group, n=56). Comparisons of clinical symptom scores and main pulmonary function indicators between the two groups were carried out before treatment and at 6 and 12 months after treatment. The growth velocity and changes in body mass index (BMI) were observed in the two groups.

RESULTSAt 6 and 12 months after the treatment, the standard group had significantly reduced clinical symptom scores and significantly increased pulmonary function indicators (percentage of predicted peak expiratory flow, PEF%; percentage of forced expiratory volume in 1 second, FEV1%) (P<0.05); the intermittent group had significantly reduced clinical symptom scores and significantly increased FEV1% (P<0.05), but PEF% was significantly increased only at 6 months after treatment (P<0.05). At 12 months after treatment, the standard group had significantly lower clinical symptom scores and significantly higher PEF% and FEV1% when compared with the intermittent group (P<0.05). The growth velocity and BMI showed no significant differences between the two groups at 6 and 12 months after treatment (P>0.05).

CONCLUSIONSCompared with intermittent inhalation, long-term regular inhalation of SM/FP performs better in controlling clinical symptoms and enhancing pulmonary function in children with asthma. Inhalation of SM/FP for one year reveals no apparent effect on the growth and development of these children.

Administration, Inhalation ; Adrenal Cortex Hormones ; administration & dosage ; Asthma ; drug therapy ; Body Mass Index ; Child ; Child Development ; drug effects ; Child, Preschool ; Female ; Humans ; Male

OBJECTIVE: To determine the association between perioperative anesthetic exposure and neurodevelopmental status at age 1 year old baby underwent complex cardiac surgery.
 METHODS: One hundred and fifteen infants were selected from Sichuan People's Hospital. A cohort study was conducted on neonates who underwent complex cardiac surgery. The babies were performed brain MRI before the operation and 7 days after the operation, and 12-month neurodevelopmental testing was carried out with Bayley Scales of Infant and Toddler Development (the third Edition, Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the 12 months. The association between peri-operative anesthetic exposure and 12-month neurodevelopmental status were analyzed.
 RESULTS: A total of 92 infants were enrolled for the final analysis. Their Bayley-III scores of cognitive, language, and movement were as follows: 104.2 ± 14.7, 85.6 ± 11.3, and 86.9 ± 13.5, respectively. MRI results showed that 17 infants showed pre-operative brain injury and 25 infants showed new post-operative injury. After performing the analysis of stepwise multivariable linear regression, MRI showed the factors affecting neurodevelopment of newborn include the new post-operative injury, higher VAA exposure, fentanyl dose, benzodiazepine dose, ICU length of stay, pre-operative mean regional cerebral oxygen saturation (rSO₂), and abnormal chromosomes.
 CONCLUSION VAA exposure and ICU length of stay are associated with poor neurodevelopmental scores at 12 months of age. Further studies need to identify the potential modifiable factors in the peri-operative care of neonates to improve neurodevelopmental outcomes.
Anesthetics ; adverse effects ; Benzodiazepines ; adverse effects ; Cardiac Surgical Procedures ; Child Development ; drug effects ; Cohort Studies ; Fentanyl ; adverse effects ; Humans ; Infant ; Infant, Newborn ; Length of Stay ; Linear Models ; Magnetic Resonance Imaging ; Neuroimaging

OBJECTIVETo evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.

METHODSixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.

RESULT(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.

CONCLUSIONIntermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.

Body Height ; drug effects ; Bone Development ; Child ; Child Development ; drug effects ; Drug Therapy, Combination ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; therapeutic use ; Growth Disorders ; drug therapy ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology ; Stanozolol ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the clinical effects of the early use of recombinant human erythropoietin (rhEPO) on the neurointelligence development in very low birth weight infants (VLBWI).

METHODSSeventy-eight VLBWI were divided into rhEPO treatment group (n=35) and control group (n=43) according to the choice of their parents. Neonatal behavioral neurological assessment (NBNA) was performed at 40 weeks of corrected gestational age. The Gesell Developmental Schedules were used for neurodevelopmental evaluation at 3, 6, and 12 months of corrected age. The abnormal rates of auditory brainstem response (ABR) and cranial ultrasound were evaluated at 6 months of corrected age.

RESULTSThe rhEPO treatment group had significantly higher NBNA scores at 40 weeks of corrected gestational age than the control group (P<0.05). The adaptability at 3 months of corrected age, the gross motor, adaptability, and sociability at 6 months, and the gross motor, adaptability, fine motor, sociability, and language at 12 months were significantly better in the rhEPO treatment group than in the control group (P<0.05). The abnormal rates of ABR and cranial ultrasound in the rhEPO treatment group were significantly lower than in the control group at 6 months of corrected age (P<0.05).

CONCLUSIONSEarly use of rhEPO can promote the early recovery of neurological symptoms and improve the cognitive, motor, and language abilities in VLBWI due to its protective effects on the nervous system.

Child Development ; drug effects ; Erythropoietin ; pharmacology ; Evoked Potentials, Auditory, Brain Stem ; Female ; Humans ; Infant, Newborn ; Infant, Very Low Birth Weight ; growth & development ; Intelligence ; drug effects ; Male ; Nervous System ; drug effects ; growth & development ; Recombinant Proteins ; pharmacology

OBJECTIVETo compare differences in the intelligence and physical developmental levels of children with congenital hypothyroidism (CH) who received initial treatment at different times.

METHODSForty-nine children with CH diagnosed by neonatal screening between September 2008 and September 2011 were enrolled in this study. According to the timing of initial treatment with thyroid hormone, they were classified into two groups: <1 month and 1 to 3 months of life. At 6 months old, 1 year and 2 years old, their intelligence levels were evaluated by Gessell test. Their physical developmental levels were also measured. Their thyroid functions were examined with fluorescence immunoassay.

RESULTSWith treatment, there were no significant differences in thyroid hormones (FT3, FT4 and TSH) between the two groups (P>0.05) at 6 months old, 1 year and 2 years old. However, heights and weights in the <1 month treatment group were significantly higher than in the 1 to 3 months treatment group at all time points (P<0.05). At 6 months old, intelligence developmental levels in the <1 month treatment group were better than the 1 to 3 months treatment group (P<0.05) but significant differences were not noted at 1 and 2 years old (P>0.05).

CONCLUSIONSThe timing of initial treatment with thyroid hormone appears to be associated with the intelligence and physical development in children with CH. Treatment starting at less than 1 month of life contributes to improved physical and intelligence development compared with treatment starting at 1 to 3 months of life.

Body Height ; Body Weight ; Child Development ; drug effects ; Child, Preschool ; Congenital Hypothyroidism ; drug therapy ; physiopathology ; psychology ; Female ; Humans ; Infant ; Intelligence ; drug effects ; Male ; Thyroxine ; therapeutic use