Pediatric Investigation最新文献

Importance: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder mainly affecting the central nervous system and autoimmunity. However, research on AGS among Chinese patients is limited.

Objective: To summarize the neurologic phenotypes and genetic causes in pediatric AGS patients, providing insights for early recognition and diagnosis in the Chinese population.

Methods: Clinical features and neuroimaging results of the patients diagnosed with AGS from Beijing Children's Hospital between January 2018 and January 2022 were collected. Whole exome sequencing was used for genetic analysis.

Results: A total of 15 patients was included, all presenting with various neurological symptoms, including developmental delay (100%), motor skill impairment (100%), language disability (78.6%), dystonia (93.3%), microcephaly (73.3%), sleep disorders (26.7%), regression (20.0%), vessel disease (6.7%), and epilepsy (6.7%). Neuroimaging revealed intracranial calcification (86.7%), cerebral atrophy (73.3%), and leukodystrophy (73.3%). Seven genes were identified, with TREX1 being the most common (40.0%, 6/15), followed by IFIH1 (20.0%, 3/15). Variant c.294dupA (p.C99Mfs*3) was detected in four unrelated patients, accounting for 66.7% (4/6) patients with the TREX1 variant. A literature review showed that TREX1 gene mutations in 35.6% (21/59) of AGS patients among the Chinese population.

Interpretation: Neurological symptoms are the most prevalent and severe presentation of AGS. Diagnosis may be considered when symptoms such as developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy emerge. TREX1 mutations are predominant in the Chinese population.

Importance: Tongue tie (TT) is a condition that can cause infant feeding difficulties due to restricted tongue movement. When TT presents as a significant barrier to breastfeeding, a frenotomy may be recommended. Universally accepted diagnostic criteria for TT are lacking and wide prevalence estimates are reported. New referral processes and a Frenotomy Assessment Tool were implemented in one Canadian health region to connect breastfeeding dyads with a provider for TT evaluation and frenotomy.

Objective: To determine the proportion of babies with TT as well as the frequency of frenotomy.

Methods: This cross-sectional study included infants who initiated breastfeeding at birth and were referred for TT evaluation over a 14-month period. Data were collected retrospectively by chart review and analyzed using SPSS. Factors associated with frenotomy were examined using logistic regression.

Results: Two hundred and forty-one babies were referred. Ninety-two percent (n = 222) were diagnosed with TT and 66.0% (n = 159) underwent frenotomy. In the multivariate model, nipple pain/trauma, inability to latch, inability to elevate tongue, and dimpling of tongue on extension were associated with frenotomy (P < 0.05). Most referrals in our region resulted in a diagnosis of TT; however, the number of referrals was lower than expected, and of these two-thirds underwent frenotomy.

Interpretation: TT is a relatively common finding among breastfed infants. Future research should examine whether a simplified assessment tool containing the four items associated with frenotomy in our multivariate model can identify breastfed infants with TT who require frenotomy.

The onset of critical rare diseases (RDs) in children is rapid and dangerous, accompanied by a high mortality rate, which brings a heavy burden to both families and society. Multiple malformations, neuromuscular diseases, metabolic diseases, and heart diseases are the most common types of RDs in children of China, often manifesting with multiple organ dysfunction. At present, the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time, a high misdiagnosis rate, limited treatment modalities, and a significant disease burden. However, with the progress in genetic testing technology, the establishment of multidisciplinary diagnosis and treatment platforms, and the implementation of relevant RD policies in China, children with critical RDs will received enhanced medical services, experience improved prognoses, and reintegrate into social life.

Importance: Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported.

Objective: This study aims to explore the appropriate eltrombopag concentration in pediatric ITP.

Methods: This was a single-center, prospective cohort study. Children diagnosed with refractory persistent/chronic ITP and platelet count < 30×10⁹/L were treated with eltrombopag and followed up for at least 2 months. Concentration was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics-concentration, concentration-response, and concentration-ADRs were analyzed.

Results: A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45‒94) months. The median dose and concentration were 1.39 (1.09‒1.56) mg/kg and 2.70 (2.25‒4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755, P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538, P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56‒1.00). Youden's index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response.

Interpretation: Eltrombopag proves efficacious and well-tolerated for treating pediatric ITP. However, prolonged and high-dose administration may increase the likelihood of ADRs. Thus, examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.

Importance: In 2019, Nigeria had the largest number of under-5 child deaths globally and many of these deaths occurred within the first week of life. The World Health Organization recommends infant postnatal care (PNC) attendance to support newborn survival; however, utilization of PNC is known to be low in many contexts.

Objective: This study examined coverage and individual-level determinants of infant PNC attendance in Nigeria.

Methods: Nigeria Demographic Health Survey (NDHS) 2018 data were used to evaluate infant PNC coverage and determinants. Infant PNC was defined as receipt of care within 2 days of birth. Children delivered up to 2 years before the 2018 NDHS were included. We examined predictors of infant PNC with modified Poisson regression models to estimate relative risks (RRs).

Results: The national coverage of infant PNC was 37.3% (95% confidence interval [CI]: 35.8%-38.7%). Significant heterogeneity in PNC attendance existed at state and regional levels. Facility delivery was strongly associated with the uptake of PNC (RR: 6.07; 95% CI: 5.60-6.58). Greater maternal education, maternal employment, urban residence, female head of household, and greater wealth were also associated with an increased likelihood of PNC visits.

Interpretation: The uptake of infant PNC is low and interventions are urgently needed to promote equity in access and increase demand for PNC in Nigeria.