The fetal outcomes after neoadjuvant platinum and paclitaxel chemotherapy during pregnancy: analysis of three cases and review of the literature.

OBJECTIVE: Data on the outcomes of fetus who are exposed to neoadjuvant platinum and paclitaxel chemotherapy during pregnancy are lacking. METHODS: Relevant data were abstracted from patients in our institution, PubMed, Embase and Cochrane Library databases. The primary assessment was the frequency of fetal death and congenital abnormalities. The secondary assessment was other negative fetal/infant outcomes including FGR, RDS, secondary malignant diseases and other recorded adverse events. RESULTS: Of the three infants in our center who exposed to platinum and paclitaxel chemotherapy during pregnancy, the physical evaluation and qualified Denver Developmental Screening Test showed normal findings at the last follow-up (19-24 months). Hearing evaluation among three children also showed normal findings. Another 34 infants (including a twins) of 21 studies in previous studies who exposed to platinum and paclitaxel chemotherapy during pregnancy were included in the final analysis. Of the 37 infants identified, 24 were exposed to cisplatin plus paclitaxel, and 13 were exposed to carboplatin plus paclitaxel. None of the 37 fetuses was abortion or dead during the pregnancy. 97.3% (36/37) infants were delivered by cesareans and the median gestational ages of delivery were 34.76 weeks (95% CI, 34.08-35.44). 1 fetus showed intrauterine growth restriction and one was found with left-sided ventriculomegaly and hydramnios before chemotherapy. Adverse events occurred in 18.9% (7/37) infants at birth, including two RDS, one hearing loss, one pathological jaundice, one first-degree intraventricular hemorrhage, one erythema, one corresponding to -0.5 standard deviation from average body weight of the same gestational weeks. No reports of neonatal cardiologic abnormalities are reported in these infants after the initiating of chemotherapy. The infant with congenital anomaly died 5 days after birth. During the follow-up, 5.4% (2/37) of the infants were diagnosed with malignant diseases. One retroperitoneal embryonal rhabdomyosarcoma at 5 years old and one acute myeloid leukemia at 22 months of age. 32/37 (86.5%) children were healthy at the end of follow-ups (median 33 months, IQR 15.75-54.25 months). CONCLUSIONS: Our results showed that neoadjuvant platinum and paclitaxel combined chemotherapy was a feasible and safe choice for the management of patients with cervical and ovarian cancer during the second and third trimesters of gestation.

Body composition during early infancy and developmental progression from 1 to 5 years of age: the Infant Anthropometry and Body Composition (iABC) cohort study among Ethiopian children.

Early nutrition and growth have been found to be important early exposures for later development. Studies of crude growth in terms of weight and length/height, however, cannot elucidate how body composition (BC) might mediate associations between nutrition and later development. In this study, we aimed to examine the relation between fat mass (FM) or fat-free mass (FFM) tissues at birth and their accretion during early infancy, and later developmental progression. In a birth cohort from Ethiopia, 455 children who have BC measurement at birth and 416 who have standardised rate of BC growth during infancy were followed up for outcome variable, and were included in the statistical analysis. The study sample was restricted to mothers living in Jimma town who gave birth to a term baby with a birth weight ≥1500 g and no evident congenital anomalies. The relationship between the exposure and outcome variables was examined using linear-mixed regression model. The finding revealed that FFM at birth was positively associated with global developmental progression from 1 to 5 years (ß=1·75; 95 % CI 0·11, 3·39) and from 4 to 5 years (ß=1·34; 95 % CI 0·23, 2·44) in the adjusted model. Furthermore, the rate of postnatal FFM tissue accretion was positively associated with development at 1 year of age (ß=0·50; 95 % CI 0·01, 0·99). Neither fetal nor postnatal FM showed a significant association. In conclusion, fetal, rather than postnatal, FFM tissue accretion was associated with developmental progression. Intervention studies are needed to assess whether nutrition interventions increasing FFM also increase cognitive development.

Long-term safety and efficacy of telbivudine in infants born to mothers treated during the second or third trimesters of pregnancy.

Telbivudine, an FDA pregnancy category B drug, has been found to reduce hepatitis B virus (HBV) perinatal transmission with no safety concerns in infants aged up to 1 year. This study evaluated the long-term efficacy and safety of telbivudine in 214 infants born to 210 pregnant women with chronic hepatitis B infection who were treated with telbivudine during pregnancy (weeks 20-32 of gestation). The infants were followed for up to 5 years after birth. The efficacy endpoint was the rate of perinatal transmission, which was established by HBsAg and HBV DNA levels at 7 and 12 months. Safety endpoints included head circumference, weight, height, congenital abnormality and hospitalization rates. In addition, the Denver Developmental Screening Test was performed in 92 randomly selected infants. None of the 214 infants born to these women were infected with HBV, and all had effective serum hepatitis B surface antibody (HBsAb) levels. Compared with Chinese standard values, there were few differences in the infants' mean head circumference, weight, and height values. No birth defects were diagnosed, and the congenital abnormality rate was 0.934%. Serious adverse events requiring hospitalization occurred in 20 infants (9.35%). The qualified Denver Developmental Screening Test rate in 92 infants was 97.82%, which was comparable to a rate of 92% in normal Chinese children. Thus, treatment with telbivudine during the second or third trimesters of pregnancy safely blocked perinatal transmission of HBV. Infants born to telbivudine-treated mothers showed normal growth and development during long-term follow-up of up to 5 years.

Early aggressive nutrition enhances language development in very low-birthweight infants.

BACKGROUND: Inadequate nutrition in very-low-birthweight (VLBW) infants is known to be associated with growth failure and poor neurological outcomes. We aimed to investigate the association of early aggressive protein and energy intakes with weight gain and 18-month neurodevelopmental outcomes in VLBW infants. METHODS: A total of 90 infants among 129 infants who survived to discharge were included and divided into two groups (early aggressive nutrition [n = 52] vs conventional nutrition [n = 38]). Clinical findings were compared between the two groups and daily protein and energy intakes were collected for the first 4 weeks of life. Multiple regression analyses tested the association between weekly protein or energy intakes and the result of each category of the Denver Developmental Screening Test II at 18 months' corrected age or weight gain. RESULTS: The early aggressive nutrition group had higher rates of normal language development and lower rates of growth failure (<10th percentile) at both 40 weeks' and 18 months' corrected age compared to the conventional nutrition group. After controlling for the confounding variables, higher first week protein and energy intakes each independently contributed to normal language development (odds ratio [95% confidence interval]; 9.4 [1.8-49.6] per 1 g/kg of protein increase and 1.7 [1.1-2.8] per 10 kcal/kg of energy increase). Higher first-week protein intake was associated with a higher weight at 40 weeks' corrected age (r = 0.41, P = 0.005). CONCLUSIONS: This study demonstrates the importance of the protein and energy intakes in VLBW infants in the first week of life not only for growth but also for better language development.

Neurodevelopmental Assessment in Children With Congenital Heart Disease by Applying the Denver Developmental Screening Test 2: A Prospective Cross-Sectional Study.

Background Congenital heart conditions often cause developmental delays and impact neurodevelopment throughout one's lifetime. Hence, it is crucial to analyze the impact that heart defects have on the developing brain of a child. The present cross-sectional study was undertaken given the paucity of studies on the developmental status in children with congenital heart diseases (CHDs) in central India, where we tried to evaluate and compare the prevalence of neurodevelopmental delay in individuals with different congenital cardiac disorders. The objectives of our study were, firstly, to utilize the Denver Developmental Screening Test 2 (DDST-2) to evaluate the neurodevelopmental conditions in children with CHD; secondly, to compare the neurodevelopmental state of children with acyanotic CHD (ACHD) and cyanotic CHD (CCHD); and thirdly, to ascertain the prevalence of developmental delay in children with CHD. Methodology The study population comprised children aged six months to six years with two-dimensional (2D) echocardiography confirmation of CHD; those who were critically ill, had genetic syndromes, and were not willing to participate in the study were excluded. The neurodevelopmental assessment was conducted using the DDST-2. The screening looked at each patient's progress in four areas: personal-social, fine motor-adaptive, language, and gross motor. Based on these observations, results were obtained and interpreted. Result Out of 82 children with CHD, the prevalence rate of developmental delay according to the DDST-2 was found to be maximum in the gross motor domain and the least affected in the social domain, which was similar to the analysis of developmental delay by developmental quotient (DQ). The comparative analysis of developmental delay in ACHD and CCHD according to the DDST-2 showed a significant P value only in the gross motor domain. Conclusion The DDST-2 is a straightforward screening tool for determining how well-developed infants with CHD are. The gross motor domain is the most frequently damaged in ACHD and CCHD, followed by the fine motor domain, and the social domain is the least affected. Cyanotic CHD patients are more susceptible to developmental delay than children with ACHD.

Developmental outcomes in children from cryopreserved embryos compared to their siblings from fresh embryo transfers: a case series.

OBJECTIVE: This study aimed to evaluate the developmental outcomes in children from cryopreserved embryos, with minimum influences of interparental variation that would cause potential bias. Hence we examined siblings, in which the older sibs were from fresh embryo transfers, while the younger sibs were from cryopreserved embryos. METHODS: Three pairs of siblings were evaluated. All routine prenatal and neonatal evaluation were performed, while personal-social, language, fine and gross motor evaluation were all evaluated by the Denver Developmental Screening Test (DDST)-II. Wechsler Preschool and Primary Scale of Intelligence (WPPSI) test was used to measure the Intelligent Quotient (IQ) in 5 of 6 children. RESULTS: Standard prenatal measurements of all children suggested uneventful pregnancies, followed by uneventful deliveries. DDST-II results showed that the aspects of personal-social, language, fine and gross motor in every child are as expected according to their ages. Results from WPPSI tests suggest that 5 of 6 evaluated children acquired average to high-average intelligences. CONCLUSIONS: The results suggest that the developmental outcomes in children from cryopreserved embryos have no significant differences with the outcomes in children from fresh embryo transfers.

Evaluation of the developmental outcome in children with congenital hypothyroidism.

BACKGROUND: Congenital hypothyroidism (CH) is one of the most common endocrine diseases and one of the major causes of mental retardation in children. So we aimed to evaluate the developmental outcome of children with CH. METHODS: This case-control study was performed on two 3-6-year-old groups of 100 patients. The case group was children with CH, referred to Endocrine Clinic of Amirkola Children's Hospital (2011-2017) and the control group was healthy children and normal from other states. The Denver developmental screening test-II (DDST_II) was used to assess the developmental factors and disorders in four areas of gross motor, fine motor, personal-social and language. Data were analyzed by SPSS 21 using descriptive statistics, t-test and chi-square, and a p<0.05 was considered significant. RESULTS: The mean age of 200 children in the case and control groups was 54.62±15.72 and 59.68±15.64 months, respectively. In the case group, 45% and 55% of them had transient and permanent CH, respectively. All four criteria of DDST_II in the control group as well as gross motor in the case group were normal, but fine motor, personal-social and language were reported normal in 94, 95 and 93% of the case group, respectively. All subjects with abnormal DDST_II, had a negative neonatal screening tests. CONCLUSION: The results obtained from DDST_II indicated that 6% of children with CH had an abnormal development, all who had an onset of medical treatment over 30 days, which makes it important to screen the neonatal thyroid disease and diagnose this disease timely.

Corpus callosotomy for treatment of drug-resistant epilepsy: a review of 16 pediatric cases in northern Vietnam.

OBJECTIVE: The aim of this study was to evaluate postoperative seizure outcome in children with drug-resistant epilepsy not eligible for focal resection who underwent corpus callosotomy. METHODS: The study included 16 patients undergoing corpus callosotomy between September 2015 and May 2018. Seizure semiology and frequency, psychomotor status, and video electroencephalography and imaging findings were evaluated for all patients. RESULTS: Of the 16 patients who underwent callosotomy during the study period, 11 underwent complete callosotomy and 5 underwent anterior only. Seizure improvement greater than 75% was achieved in 37.5% of patients, and another 50% of patients had seizure improvement of 50%-75%. No sustained neurological deficits were observed in these patients. There were no significant complications. Duration of postoperative follow-up ranged from 12 to 44 months. CONCLUSIONS: Corpus callosotomy is an effective treatment for selected patients with drug-resistant epilepsy not eligible for focal resection in resource-limited settings. Fostering and developing international epilepsy surgery centers should remain a high priority for the neurosurgical community at large.

Structural changes in the brain on cranial magnetic resonance imaging in severely malnourished children before and after treatment.

OBJECTIVE: The aim of this study was to examine the structural changes in brain on magnetic resonance imaging (MRI) in severely malnourished children before and after treatment. METHODS: This was a prospective study conducted at a Severe Malnutrition Treatment Unit (SMTU) at a tertiary care center. The study was carried out with 52 severely malnourished children 0 to 5 y of age admitted to the SMTU. The cases with neurologic diseases such as epilepsy, cerebral palsy, meningitis, tumor, or hydrocephalus; or history of perinatal asphyxia were excluded to enable us to detect central nervous system changes attributable to malnutrition only. MRI brain without contrast was performed on all 52 cases at admission and after 6 mo of treatment and were reported by an experienced radiologist. The common MRI findings in the study included cerebral atrophy, dilated ventricles, periventricular white matter changes, widened cortical sulci, enlarged basal cisterns, and widened interhemispheric fissure. Development assessment using the Denver Developmental Screening Test II was also performed to infer correlation with MRI findings. RESULTS: Of the 52 children who were severely malnourished, 10 (i.e., 19.2%) had abnormal MRI findings. Development assessment revealed that of the 10 abnormal MRI cases, 80% had delayed developmental milestones as well. These changes are reversible in most cases after nutritional rehabilitation. CONCLUSIONS: The present study revealed that malnutrition per se has a significant effect on the structure of the developing brain and also affects neurologic development. These changes are reversible after treatment so early stimulation and nutritional rehabilitation can help to prevent permanent neurologic derangements.

Evaluation of neurodevelopment of children with congenital hypothyroidism by the Denver Developmental Screening Test.

BACKGROUND: Thyroid hormones are essential for growth and brain development in childhood. Although congenital hypothyroidism (CH) is the most common reason for mental retardation, normal neurological development can be achieved through early and effective treatment. The aim of the present study was to evaluate the neurological development of CH patients aged 24-56 months. METHODS: The study included a total of 116 healthy control subjects and 112 patients aged 24-56 months who were diagnosed with CH during the neonatal period and were being followed up at the Pediatric Endocrinology Department, Keçiören Training and Research Hospital, between 2012 and 2015. Demographics and clinical data of interventions and outcomes were retrieved for each patient. Statistical analysis was performed using an unpaired Student's t-test to compare means and χ2-analysis to compare proportions. RESULTS: There were no significant differences between the CH and control groups with respect to gestational age, birth weight, height standard deviation scores (HSDS) and body weight standard deviation scores (BWSDS) (p>0.05). When the groups were compared according to the Denver Developmental Screening Test (DDST), no significant differences were found in terms of personal-social, fine motor skills, or language development (p=0.325, p=0.087 and p=0.636, respectively). However, a significant difference was found between the two groups with respect to gross motor development and the result of the DDST (p=0.001). No statistical difference was found between the control and patient groups on the day of starting treatment but the number of patients with an abnormal result in the DDST starting treatment at >15 days was found to be significantly higher than the number of patients starting treatment ≤15 days. No associations were found between the DDST results of the CH group and the following factors: initial L-thyroxine (LT4) level, initial LT4 dose and the onset of treatment. CONCLUSIONS: The findings of this study indicate that the DDST results in patients with CH are generally good. Initiating treatment immediately after diagnosis and during the first days of life is absolutely imperative. However, in contrast to timing, we could not find strong evidence for determining the precise optimal dosage of LT4 to initiate treatment in children diagnosed with CH. Both the American Academy of Pediatrics and the European Society for Pediatric Endocrinology recommend 10-15 µg/kg/day as the initial dose.

The Influence of Different Caregivers on Infant Growth and Development in China.

OBJECTIVE: An increasing number of parents in China ask grandparents or babysitters to care for their children. Modern parents are often the only child in their family because of China's One-Child Policy and thus may lack interaction with siblings. Accordingly, the present study aimed to explore whether different caregivers affect the physical and development of infants in China. METHODS: In total, 2,514 infants were enrolled in our study. We assessed their weight-for-age, supine length-for-age, weight-for-length, occipital-frontal circumference, and Denver Developmental Screening Test (DDST) results and recorded their general parental information and their primary caregivers. RESULTS: The weights and lengths of 12-month-old infants under the care of babysitters were significantly lower than those of infants under the care of parents or grandparents (P < 0.05). Additionally, 12-month-old infants under the care of babysitters had the lowest DDST pass rate (75%) among the three groups (χ2 = 11.819, P = 0.012), especially for the fine motor-adaptive and language domains. Compared to 12-month-old infants under the care of parents and babysitters, infants under the care of grandparents were more likely to be overweight or obese (P < 0.001). CONCLUSION: The study showed that caregivers had a dominant role in the physical and cognitive development of the infants. Specifically, compared with infants raised by grandparents and parents, 12-month-old infants under the care of babysitters had partially suppressed lengths and weights and lagged cognitively. The 12-month-old infants under the care of grandparents were more overweight than those cared for by parents and babysitters.

Evaluation of clinical course and neurocognition in children with self-limited infantile epilepsy in a Turkish cohort study.

The outcome of children with self-limited infantile epilepsy was reported to be normal psychosocial and cognitive development as a characteristic criterion. We aimed to investigate the clinical course and neurocognitive outcome in children with self-limited infantile epilepsy in a Turkish cohort. The clinical course, electroencephalographic (EEG) characteristics, neuroimaging, treatment, and outcome of children with self-limited infantile epilepsy were retrospectively analyzed. All infants were reevaluated with the Denver Developmental Screening Test in addition to neurologic examination. Of 44 patients, self-limited familial infantile epilepsy was diagnosed in 8 infants (18.2%) and self-limited nonfamilial infantile epilepsy in 28 (63.6%). Interictal EEGs and neurologic examinations were normal in all cases. Fine motor and gross motor skills, language, adaptive personal/social skills were near-normal in all patients with self-limited familial infantile epilepsy. Delay in language parameters was observed in 2 infants with self-limited nonfamilial infantile epilepsy. Language skills should be thoroughly evaluated with detailed neurocognitive screening tests in patients with self-limited infantile epilepsy.

The impact of anemia and body mass index (BMI) on neuromotor development of preschool children

Summary Objective: According to data from the World Health Organization (WHO), anemia is a prevalent health problem that leads to increased morbidity and mortality, especially in preschool children. Anemia is recognized as a major health problem due to its negative effects on the mental and physical development during childhood. The aim of our study was to determine the levels of anemia of children in a kindergarten affiliated to the Directorate of National Education using a non-invasive method, and to investigate the effects of anemia on the physical, mental and neuromotor development of children. Method: The levels of anemia was evaluated by using a non-invasive measurement device. Data collection was performed by means of a questionnaire to evaluate the children's physical development and set Denver Developmental Screening Test II scores. Results: Our findings show that 21% of non-anemic and 15% of anemic children are in the suspected abnormal group according to their DDST II total score. Furthermore, it has been identified that mild anemia has a positive effect on neuromotor development, while overweight and obesity affect neuromotor development in a negative way. Conclusion: According to the results obtained from the study, mild anemia may have a positive effect on the children's neuromotor development, while malnutrition could have a negative impact.

A comparison of the korean-ages and stages questionnaires and denver developmental delay screening test.

OBJECTIVE: To evaluate concurrent validity between the Korean-Ages and Stages Questionnaires (K-ASQ) and the Denver Developmental Screening Test II (DDST II), and to evaluate the validity of the K-ASQ as a screening tool for detecting developmental delay of Korean children. METHOD: A retrospective chart review was done to examine concurrent validity of the screening potentials for developmental delay between the K-ASQ and the DDST II (n=226). We examined validity of the K-ASQ compared with Capute scale (n=141) and Alberta Infant Motor Scale (AIMS) (n=69) as a gold standard of developmental delay. Correlation analysis was used to determine the strength of the associations between tests. RESULTS: A fair to good strength relationship (k=0.442, p<0.05) was found between the K-ASQ and the DDST II. The test characteristics of the K-ASQ were sensitivity 76.3-90.2%, specificity 62.5-76.5%, positive likelihood ratio (PLR) 2.41-3.40, and negative likelihood ratio (NLR) 0.16-0.32. CONCLUSION: Evidence of concurrent validity of the K-ASQ with DDST II was found. K-ASQ can be used for screening of developmental delay.