Case Report: A Very Low Birth Weight Female Infant With Congenital Bilateral Periventricular Leukomalacia, Born to a Mother With Coronavirus Disease 2019.

A 26-year-old primipara woman with COVID-19 performed an emergency Cesarean section due to further hypoxemia at 28 weeks 5/7 days gestation. The female neonate was born weighing 1,347 gram with an Apgar score of four at 1 min, three at 5 min, and eight at 10 min. RT-PCR from nasopharyngeal swabs for COVID-19 were performed at birth, 24 h, and 48 h after birth, all of which were negative. On head ultrasound bilateral cystic lesions were found in the anterior horn of the lateral ventricles at birth. A brain magnetic resonance imaging (MRI) test at 56 days of life (corrected 36 weeks and 6/7 days) revealed cystic lesions with T1 low signal, T2 high signal, and T2 Flair high signal around the anterior horn of the lateral ventricle and We diagnose it as Grade 2 periventricular leukomalacia (PVL). She was discharged on day 64 of life, with no abnormality on exam. While the majority of neonates born to women with COVID-19 during pregnancy have favorable outcome, we report a case of a neonate with Grade 2 periventricular leukomalacia and this should prompt clinicians to monitor fetal cerebral function and structure shortly after birth.

Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations.

RASopathies are autosomal dominant disorders caused by mutations in more than 10 known genes that regulate the RAS/MAPK pathway. Noonan syndrome (NS) is a RASopathy characterized by a distinctive facial appearance, musculoskeletal abnormalities, and congenital heart defects. We have recently identified mutations in RIT1 in patients with NS. To delineate the clinical manifestations in RIT1 mutation-positive patients, we further performed a RIT1 analysis in RASopathy patients and identified 7 RIT1 mutations, including two novel mutations, p.A77S and p.A77T, in 14 of 186 patients. Perinatal abnormalities, including nuchal translucency, fetal hydrops, pleural effusion, or chylothorax and congenital heart defects, are observed in all RIT1 mutation-positive patients. Luciferase assays in NIH 3T3 cells demonstrated that the newly identified RIT1 mutants, including p.A77S and p.A77T, and the previously identified p.F82V, p.T83P, p.Y89H, and p.M90I, enhanced Elk1 transactivation. Genotype-phenotype correlation analyses of previously reported NS patients harboring RIT1, PTPN11, SOS1, RAF1, and KRAS revealed that hypertrophic cardiomyopathy (56 %) was more frequent in patients harboring a RIT1 mutation than in patients harboring PTPN11 (9 %) and SOS1 mutations (10 %). The rates of hypertrophic cardiomyopathy were similar between patients harboring RIT1 mutations and patients harboring RAF1 mutations (75 %). Short stature (52 %) was less prevalent in patients harboring RIT1 mutations than in patients harboring PTPN11 (71 %) and RAF1 (83 %) mutations. These results delineate the clinical manifestations of RIT1 mutation-positive NS patients: high frequencies of hypertrophic cardiomyopathy, atrial septal defects, and pulmonary stenosis; and lower frequencies of ptosis and short stature.

Gastroesophageal reflux related to respiratory inhibition after crying and feeding hypoxemia in infants.

OBJECTIVE: To determine the relationships between gastroesophageal reflux (GER) and both respiratory inhibition after crying (RIAC) and feeding hypoxemia in infants. METHODS: We screened for RIAC and feeding hypoxemia among infants with a gestational age of 36 weeks or greater using pulse oximetry. We investigated the infants who showed hypoxemia with a decrease in SpO2 to less than 70% and bradycardia with a heart rate of less than 100 beats per minute caused by GER. We then evaluated the relationships between these events and both RIAC and feeding hypoxemia. RESULTS: We examined 250 infants in the present study. RIAC and feeding hypoxemia were observed in 35 (14.0%), and 30 (12.0%) infants, respectively. Ten infants showed hypoxemia and bradycardia caused by GER. These events were correlated with RIAC (p = 0.006) and feeding hypoxemia (p = 0.031). CONCLUSIONS: In the infants with RIAC and feeding hypoxemia, some show severe hypoxemia and bradycardia caused by GER. Medical staff caring for infants should note the presence of RIAC and feeding hypoxemia.

Respiratory inhibition after crying and feeding hypoxemia in infants.

OBJECTIVE: To determine the incidence, risk factors and natural history of respiratory inhibition after crying (RIAC) and feeding hypoxemia. METHODS: We screened for RIAC and feeding hypoxemia among 393 infants with a gestational age ≥ 36 weeks using pulse oximetry. Twenty-seven infants were treated in the neonatal intensive care unit. RESULTS: RIAC and feeding hypoxemia were observed in 95 (24.2%) and 124 (31.6%) infants, respectively. RIAC correlated with feeding hypoxemia (p < 0.001), grade II increased echogenicity in the ganglionic eminence (p = 0.005), dilation of the lateral ventricle (p = 0.044), threatened premature labor (p = 0.033) and twin gestation (p = 0.089). Feeding hypoxemia correlated with RIAC (p < 0.001), abnormal cranial ultrasound findings (p < 0.001), maternal smoking during pregnancy (p = 0.083), asymmetric intrauterine growth restriction (p = 0.012) and twin gestation (p = 0.067). All infants recovered from RIAC in an average of 4.5 (2.0-7.0) d. Fifteen infants recovered from feeding hypoxemia, but 10 infants needed additional assistance and monitoring by nursing until the day of discharge. The day of discharge was day 8.0 (5.0-12.4). CONCLUSIONS: RIAC and feeding hypoxemia are observed among healthy infants, and these infants experience repeated events of prolonged hypoxemia.

Asymmetric intrauterine growth restriction is a risk factor for respiratory inhibition after crying in infants.

OBJECTIVE: We investigated whether intrauterine growth restriction (IUGR) correlated with respiratory inhibition after crying (RIAC) and feeding hypoxemia. METHODS: We screened for RIAC among 1248 infants with a gestational age ≥36 weeks using our established method with cranial ultrasound, SpO2 monitoring, and polygraphy. We classified the infants into three groups: symmetric IUGR, asymmetric IUGR, and control. We compared the perinatal factors with the incidence of RIAC and feeding hypoxemia among the three groups. RESULTS: Overall, 26 infants had symmetric IUGR, 143 infants had asymmetric IUGR, and 1079 infants were in the control group. RIAC was observed in 10 (6.9%) infants in the asymmetric IUGR group and in 37 (3.4%) infants in the control group. Feeding hypoxemia was observed in 15 (10.5%) infants in the asymmetric IUGR group and in 52 (4.8%) infants in the control group. The incidence of RIAC and feeding hypoxemia in the asymmetric IUGR group was significantly more than that in the control group. None of the infants with symmetric IUGR exhibited RIAC or feeding hypoxemia. CONCLUSIONS: The results indicate that asymmetric IUGR is a risk factor for RIAC and feeding hypoxemia. These infants should be aggressively screened for RIAC.

Polygraphic findings of 47 cases with respiratory inhibition after crying.

OBJECTIVE: To report the polygraphic findings of infants with respiratory inhibition after crying (RIAC). METHODS: We screened for RIAC among infants with a gestational age ≥36 weeks using our established method with cranial ultrasonography, SpO(2) monitoring and polygraphy. RIAC is defined as central apnea that occurred immediately after crying with a decrease in SpO(2) to <60%, followed by repeated irregular respiration and apnea as the respiration gradually recovered. The subjects were infants with RIAC for whom we could study the polygraphic findings in detail. RESULTS: Forty-seven RIAC cases were included in the present analysis. The frequency of RIAC was 2.1 (1.2-7.0) times per 24 h. The maximum duration of respiratory inhibition was 78.0 (52.6-109.0) s. The maximum duration of SpO(2) <60% during RIAC was 39.0 (9.8-93.2) s. The minimum SpO(2) value during RIAC was 53.0% (42.2-58.0%). The minimum heart rate during RIAC was 103.0 (79.1-127.1) bpm. CONCLUSIONS: RIAC is observed among healthy infants, and they experience repeated prolonged hypoxemia.