Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.

Objective:To review the treatment experience of extremely premature infants (EPIs) with gestational age (GA) <23 weeks.Methods:From January to November 2021, EPIs with GA<23 weeks treated in our hospital was retrospectively analyzed.Results:A total of 3 patients with GA of 22 weeks were reviewed, including 2 boys and 1 girl. Their birth weight (BW) was 450~498 g. The duration of hospitalization was 112~126 d. The treatment included early "gentle" management strategies, respiratory management, anti-infection, patent ductus arteriosus treatment and parenteral + enteral nutrition. All 3 infants were discharged from the hospital without further oxygen therapy. All had satisfying oral feeding with no neurological sequelae on follow-up.Conclusions:Early "gentle" management is the key to successful treatment and good prognosis for EPIs with GA<23w

Objective:To analyze the cases referred to a higher-level hospital from the Department of Neonatology in a primary hospital, and evaluate the efficiency of clinical works related to the referrals.Methods:Data of neonates admitted to the Department of Neonatology at Maternal and Child Health Hospital of Dabu County from January 2018 to December 2020 and referred to the superior hospital were retrospectively analyzed.Results:A total of 1 670 neonates were included and 128 neonates were referred.The median age of the neonates referred was 0.5 hours(0 hours, 25 days), the median gestational age was 38 + 3(29 + 1, 42 + 4) weeks, the median weight was 3 000(1 250, 4 800) g, and the transport distance was 78 km.Twenty-four cases were assessed as critical cases before the referral, 125 cases were improved and discharged after treatment in the superior hospital, and three cases died.The referral rate in 2018, 2019 and 2020 showed a downward trend year by year (10.3%, 7.6% and 4.0%, respectively), and the difference was statistically significant( χ2=14.362, P=0.001). The proportion of critical cases in referral cases increased year by year (9.4%, 23.9% and 38.9%, respectively), and the difference was statistically significant( χ2=9.289, P=0.010). The incidence of critical case was higher in those whose mothers didn′t have regular prenatal examination during pregnancy( χ2=5.129, P=0.032). Conclusion:The ability of neonatal treatment in primary hospitals has been improved.The neonates need to be referred and critical cases are not rare in primary hospitals.More attention should be paid to the safety and effectiveness of the regional transport network.Also, enhancing the health awareness of residents and improving the primary medical technics are important to maximize the life safety and optimal transition of newborns.

Objective:To study the incidence and risk factors of periventricular- intraventricular hemorrhage (PIVH) in extremely preterm infants (EPI) with gestational age (GA)<28 weeks.Methods:A retrospective study was performed in 304 cases of EPI hospitalized between January 2016 and December 2018. The infants were assigned into two groups according to whether PIVH occurred. Univariate analysis and Logistic regression analysis were used to determine the risk factors of PIVH.Results:Among the 304 cases,101 (33.2%) developed PIVH and 44 (14.5%) developed severe PIVH.The incidences of PIVH and severe PIVH in EPI with birth weight (BW) <750 g were 50.6% and 31.0%. The incidences of PIVH and severe PIVH in EPI with GA<26 weeks were 51.4% and 27.5%. Logistic regression analysis revealed that advanced GA ( OR=0.697, 95% CI 0.543~0.895, P=0.005) decreased the risk of PIVH. Prolonged invasive mechanical ventilation ( OR=1.121, 95% CI 1.007~1.249, P=0.037) and use of vasoactive drugs ( OR=1.373, 95% CI 1.040~1.812, P=0.025) within the first week of life increased the risk of PIVH. Conclusions:The incidences of PIVH and severe PIVH in EPI are quite high. Smaller GA, longer use of invasive mechanical ventilation and vasoactive drugs within the first week will increase the risk of PIVH in EPI.

Objective:To study the effects of breastfeeding within 2 weeks after birth on late-onset sepsis in very low birth weight infants (VLBWI).Methods:From July 2018 to June 2019, clinical data of VLBWI (birth weight <1 500 g) born in our hospital were retrospectively reviewed. According to the proportion of breastfeeding volume in total feeding volume within 2 weeks after birth, the infants were assigned into high-proportion breastfeeding group (breastfeeding >50%), low-proportion breastfeeding group (breastfeeding ≤50%) and formula group. The incidences of late-onset sepsis among the three groups were compared using the chi-square test or Fisher's exact probability method. Logistic regression was used to analyze the effects of breastfeeding within 2 weeks after birth on late-onset sepsis.Results:The incidences of late sepsis in high-proportion breastfeeding group, low-proportion breastfeeding group and formula group were 0.4% (1/216), 8.1% (5/62) and 8.0% (2/25), respectively ( P<0.001). Logistic regression analysis showed that compared with the high-proportion breastfeeding group, the low-proportion breastfeeding group ( OR=17.844, 95% CI 2.005~158.775) and the formula group ( OR=23.261, 95% CI 1.916~282.350) had increased risks of late-onset sepsis. Conclusions:For VLBWI, high proportion breastfeeding (breastfeeding >50%) within 2 weeks after birth may reduce the risk of late-onset sepsis.

Objective:To study the risk factors of hypotension after ligation of patent ductus arteriosus (PDA) in very/extremely low birth weight infants (VLBWI/ELBWI).Method:From March 2016 to January 2021, preterm infants with birth weight <1 500 g receiving bedside PDA ligation in the neonatal intensive care unit (NICU) of our hospital were enrolled in the study. According to the occurrence of hypotension within 72 hours after ligation, the infants were assigned into non-hypotension group and hypotension group. The general status and perioperative conditions of the two groups were analyzed. Multivariate Logistic regression was used to analyze the risk factors of hypotension.Result:A total of 44 cases were enrolled, including 33 in non-hypotension group and 11 in hypotension group. Univariate analysis showed that hypotension group had significantly more cases with body weight <1 100 g during surgery and receiving preoperative high frequency oscillatory ventilation (HFOV) than non-hypotension group ( P<0.05). Multivariate Logistic regression analysis showed that weight <1 100 g during surgery ( OR=12.045, 95% CI 1.351~107.394, P=0.026) and receiving preoperative HFOV ( OR=27.832, 95% CI 1.363~568.292, P=0.031)were independent risk factors of hypotension. Conclusion:Hypotension is one of the common complications of PDA ligation in VLBWI/ELBWI. The infant's body weight during ligation and receiving preoperative HFOV are independent risk factors of hypotension.

Objective:To study the effects of early breastfeeding volume on neonatal necrotizing enterocolitis (NEC) and feeding intolerance in very low birth weight infants.Methods:This study retrospectively analyzed the clinical data of 275 cases of very low birth weight infants (birth weight<1 500 g) born in Shenzhen Maternity & Child Healthcare Hospital from June 2017 to May 2018. Based on whether breastfeeding or not and the ratio of breast milk intake over the total volume of intake within two weeks after birth, they were divided into three groups: breast milk intake>50% group (>50% group, n=199), breast milk intake≤50% group (≤50% group, n=55) and formula group ( n=21). Differences in the incidence of NEC and feeding intolerance among the three groups were analyzed using Chi-square test (or Fisher's exact test). Effects of breast milk intake on the incidence of NEC and feeding intolerance were evaluated using univariate and multivariate logistic regression analysis. Results:The incidence of NEC in the >50% group, ≤50% group and formula group was 1.5% (3/199), 27.3% (15/55) and 9.5% (2/21), respectively ( P<0.01), and the incidence of feeding intolerance was 17.6% (35/199), 56.4% (31/55) and 28.6% (6/21), respectively ( χ2=34.826, P<0.01). Univariate logistic regression analysis showed that compared with the >50% group, the risk of NEC in the≤50% and formula group increased ( OR=24.500, 95% CI: 6.755-85.594; OR=6.877, 95% CI: 1.081-43.744); that of feeding intolerance increased in the≤50% group ( OR=6.316, 95% CI: 3.293-12.113). Multivariate logistic regression analysis showed that compared with the >50% group, the risk of NEC in the≤50% and formula groups increased ( OR=28.452, 95% CI: 7.280-111.195; OR=8.610, 95% CI: 1.262-58.766); that of feeding intolerance increased in the≤50% group ( OR=7.207, 95% CI: 3.601-14.425). Conclusions:Breastfeeding accounting for more than half of the total volume of intake within two weeks after birth may reduce the incidence of feeding intolerance and NEC in very low birth weight infants.

Objective:To analyze clinical features, prognosis and risk factors of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH).Methods:Clinical data of 338 infants with BPD were collected from the neonatal intensive care unit (NICU) in Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January 2016 and December 2018. These infants were divided into PH group and non-PH group. The clinical features and prognosis were compared between these two groups by Chi-square test or nonparametric test. Risk factors for BPD-PH were analyzed with binary logistic regression model.Results:Among the 338 BPD infants, 314 had no PH (92.9%) and 24 had PH (7.1%), with an average gestational age of (27.1±1.8) weeks, and 206 were males and 132 females.PH infants had younger gestational age ((26.4±2.1) vs. (27.2±1.7) weeks, t=2.201, P=0.028) and lower birth weight ((798±255) vs. (1 003±240) g, t=4.030, P<0.01), compared to non-PH infants. Besides, duration of mechanical ventilation and non-invasive positive pressure ventilation were higher in PH group than that in non-PH group (14.3 (2.1, 43.7) vs. 0.5 (0, 4.7) d, Z=-4.553, P<0.01; 30.0 (22.5, 64.2) vs. 15.0 (7.0, 26.0) d, Z=-4.838, P<0.01). The proportions of maternal hypertension, small for gestational age (SGA), late onset sepsis, ventilator associated pneumonia, hemodynamically significant patent ductus arteriosus (hsPDA), patent ductus arteriosus (PDA) requiring ligation, severe BPD and severe extrauterine growth retardation (EUGR) were higher in PH group than those in non-PH group ((20.8% (5/24) vs. 6.4% (20/314), 33.3% (8/24) vs. 7.6% (24/314), 54.2% (13/24) vs. 7.3% (23/314), 25.0% (6/24) vs. 6.1% (19/314), 75.0% (18/24) vs. 39.2% (123/314), 45.8% (11/24) vs. 1.9% (6/314), 66.7% (16/24) vs. 7.3% (23/314), 75.0% (18/24) vs. 45.5% (143/314), all P<0.05). Multivariate logistic regression analysis showed that maternal hypertension ( OR=12.950, 95 %CI: 1.740-96.385), severe bronchopulmonary dysplasia ( OR=10.160, 95 %CI: 2.725-37.884), SGA ( OR=4.992, 95 %CI: 1.432-16.920), PDA requiring ligation ( OR=19.802, 95 %CI: 3.297-118.921), severe EUGR ( OR=20.316, 95 %CI: 2.221-185.853) were independent risk factors of BPD associated PH. In the 24 infants with PH, all 7 mild PH infants and 8 moderate PH infants survived, while 4 out of 9 severe PH infants died. Among the survivors, the longest duration of oxygen therapy was up to the corrected gestational age of 1 year and 2 months. Conclusions:PH is a severe complication of BPD, and associated with higher mortality and poor prognosis. Echocardiography screening and regular post-discharge follow up are recommended for BPD infants with risk factors of PH.

Objective:To demonstrate the post-discharge catch-up growth of extremely premature infants (EPI) within 24 months of corrected age.Methods:This study retrospectively collected the anthropomorphic measurements of 311 EPI who visited Shenzhen Maternity and Child Healthcare Hospital from August 2013 to April 2020. These infants were stratified according to gestational age at birth (GA): 23-24 +6weeks, 25-26 +6weeks, 27-27 +6weeks; and birth weight:<750 g, 750-999 g, ≥1 000 g. The anthropomorphic measurements, including weight, length, and head circumference for age, were recorded timely from discharge to 24 months of corrected age. And the growth curve stratified by GA and birth weight were fitted in both chronological age and corrected age, which were then compared with the World Health Organization Child Growth Standards for term infant (2006 version), to investigate the catch-up growth pattern of EPI. And appropriate catch-up was defined as the measurements reached the 25 th percentile of WHO growth curve. Results:In these 311 EPI, 184 were males and 127 females, with gestational age of 23-27 +6 weeks and birth weight of 480-1 430 g. Regardless of the GA and birth weight, the growth curves fitted in corrected age failed to overlap with that in chronological age by 24 months of corrected age. The growth velocity of weight, length and head circumference in both corrected and chronological age were all positively correlated with GA and birth weight: the 27-27 +6weeks group showed a preferable growth pattern than the 25-26 +6weeks group, and the curve of the 23-24 +6weeks group was most unfavorable; and the same pattern was observed between the subgroups of different birth weight. Furthermore, the GA had more significant impact on the catch-up growth pattern than birth weight did. When assessed with corrected age curve, the weight and length of both male and female EPIs achieved appropriate catch-up by 24 months, as well as the head circumference of girls; whereas, boys′ head circumference reached appropriate catch-up at the corrected age of 9 months, but fell behind the 25 th percentile after that. However, when assessed with chronological age curve, both boys and girls failed to achieve appropriate catch-up in weight, length and head circumference by age 24 months. And no matter in corrected or chronological age, all physical measurements of girls were lower than those of boys. Conclusions:The rapid catch-up growth of EPI happens within 6 months of corrected age. The lower the birth weight and gestational age, the lower the physical measurements at each corresponding month of age, and the longer it takes to achieve appropriate catch-up. Gestational age has a greater impact on the longitudinal catch-up growth than birth weight does. And girls generally grow slower than boys in either correct or actual age. Before 24 months of corrected age, the growth should be assessed with corrected age rather than chronological age.