Research of coronavirus disease (COVID-19) effects on newborns is ongoing. But the research of specific variant’s effects is none. This study analyzed the effects of the Omicron variant on the perinatal outcomes of full-term newborns during the Omicron wave period. Between December 2021 and April 2022, this study was conducted on all newborns who visited a single center. We investigated due to the Omicron maternal infection maternal pregnancy complications, delivery methods, birth week, Apgar scores, neonatal resuscitation program requirement, whether respiratory support was required until 12 h after childbirth, suspicious infectious status, and mortality depending on maternal Omicron infection.p = 0.049), respectively. The 5-min Apgar score at childbirth was 9.29 ± 0.756 and 9.78 ± 0.460 for neonates born to symptomatic and asymptomatic mothers (p = 0.019), respectively. When compared with or without maternal self-isolation, neonates requiring respiratory support 12 h after birth demonstrated a significant difference . Additionally, the presence or absence of transient tachypnea of the newborn showed a significant value .A total of 127 neonates were enrolled, and 12 were excluded based on exclusion criteria. Sixteen neonates were born to mothers with a history of Omicron COVID-19, and 99 were born to non-infectious mothers. All infected mothers became infected in the 3rd trimester. Of the 16 mothers, seven were symptomatic, and four met the isolation criteria, according to Korean guidelines. The birth weight of newborns to mothers with a history of COVID and those without was 2.958 ± 0.272 kg and 3.064 ± 0.461 kg (Owing to Omicron COVID-19, newborns were born with lower birth weight, low 5-min Apgar scores, and required respiratory support until 12 h after birth. The coronavirus disease 2019 (COVID-19) is an infectious disease, identified in December 2019, and has had a major global impact; various mutations of COVID-19 have developed since then . FurtherIn addition, it is known that the novel coronavirus 2019-nCoV) continues to mutate and that there are various mutants, each exhibiting differences in infectivity, virulence, and antigenicity. Therefore, numerous studies are being conducted for each known mutation 9-nCoV co–10.Currently, in Korea, the proportion of mothers receiving antenatal care is high, and childbirth mostly occurs in hospitals . TherefoThis study investigated the effects of Omicron COVID-19 infection on general and respiratory outcomes of full-term infants hospitalized for isolation owing to infected mothers, compared to babies who had never been infected.Between December 1, 2021, and April 30, 2022, a retrospective study was conducted on all newborns aged 37 weeks or older who were admitted to the neonatal unit of Wonju Severance Christian Hospital. Newborns who were hospitalized more than 3 d after birth or who had a congenital anomaly were excluded from the study. All mothers of newborns were tested for 2019 nCoV before delivery or within 24 h of hospitalization, using PCR . Mothers who tested negative on PCR were screened for COVID-19-related symptoms before admission Furthermore, patients with an unclear history of infection and mothers infected during wave periods of other variants were excluded from the study.The management of pregnant women with COVID-19 was based on the latest Korean Society of Pediatric Infectious Diseases guidelines . MothersAll mothers were investigated for age and complications during pregnancy, such as gestational hypertension, pre-eclampsia (G-HTN), prolonged rupture of membranes (PROM), and gestational diabetes mellitus (GDM). Based on the delivery method, the analysis was divided into vaginal delivery (VD) and cesarean section (CS). In addition, multiple fetuses, intrauterine pregnancy weeks (IUP), birth weight, Apgar score (A/S), and neonatal resuscitation program (NRP) requirements were investigated. Further, neonates were classified into small-for-gestational-age (SGA), average-for-gestational-age (AGA), and large-for-gestational-age (LGA) according to the weight by number of weeks . For all2 > 40%. In all RDS cases, surfactant inhalation was treated with intubation. Air leak was also defined as the presence of pneumomediastinum, pneumothorax, or pneumopericardium on an infantogram.Transient tachypnea of the newborn (TTN) was defined when respiratory support was required until 12 h after birth and a typical sunburst pattern was seen on the infantogram. Respiratory distress syndrome of newborn (RDS) was defined as the presence of ground grass opacities or air-bronchograms on an infantogram, and a required FiOp < 0.05.The analysis was conducted based on the mother's confirmed COVID-19 history, symptoms, and whether quarantine was enforced. Maternal age and birth weight were analyzed using a t-test, IUP (weeks), and A/S according to the Mann–Whitney U test. Chi-square verification was used to analyze the birth method, multiple fetuses, presence of oxygen at birth, presence of respiratory support until 12 h after birth and its cause, suspicious sepsis, and mortality. However, when the number was 5 or less, statistical analysis was performed using Fischer's exact test. All test values were analyzed using the SPSS 26.0 version . Statistical significance was based on A total of 127 full-term newborns were enrolled in this study. Six were excluded because they presented to the hospital 3 d after birth, and four were excluded owing to congenital anomalies . In addition, one newborn of a mother infected within the Delta variant wave period and one newborn of a mother with an unknown medical history were excluded. Of the total newborns, 60 were boys and 55 were girls. There were 16 newborns of mothers who had a history of Omicron 2019-nCoV infection and 99 babies were born to mothers who did not. All mothers were infected during the 3rd trimester. Of the mothers infected with Omicron 2019-nCoV, 7 newborns were of symptomatic mothers and 4 were of isolated mothers . Moreover, there was no significant difference in A/S, SGA ratio, LGA ratio, and twin ratio (p > 0.05).There were no significant differences in IUP at childbirth, maternal age, CS ratio, male-to-female ratio, and pregnancy complications such as PROM, G-HTN, and GDM in the presence or absence of COVID history (p = 0.049)  in the number of patients who underwent NRP, required respiratory support after 12 h of birth, or had a suspected septic condition. No mortalities were reported in either group. A total of 13 babies underwent the 2019-nCoV PCR test, and all the tests were reportedly negative on 2019-nCoV PCR performed at 24 and 48 h after birth .When comparing mothers with symptoms of upper respiratory tract infection and mothers without symptoms, the IUPs at childbirth, maternal age, the CS ratio, and the male-to-female ratio had no statistically significant difference (p = 0.019). The mean birth weights of children born to mothers with symptoms of upper respiratory tract infection and asymptomatic mothers was 2.857 ± 0.183 kg and 3.062 ± 0.450 kg, respectively, which was statistically significant (p = 0.041) . The following were not significant between the two groups: performance of NRP, the requirement for respiratory support until 12 h after birth, and suspected sepsis (p > 0.05)   The presence or absence of TTN was significant  average were 42.3% and 21%, respectively . VariousIn addition, we reported that the birth weight was significantly < 2500 g for full-term newborns of mothers with a history of COVID-19 or who were symptomatic. There was no significant difference in the ratio of SGA and LGA. In this study, all mothers were infected with COVID-19 during the 3rd trimester, near full-term. A widely known symptom of COVID is taste impairment . Third tThe 5-min A/S was significantly lower in full-term babies born to symptomatic mothers, and as in a previous study, TTN rates significantly increased in self-isolated participants and some required ventilatory support , 10. It Unlike previous studies, this study was based on the Omicron variant 2019-nCoV and its effects on newborns were analyzed. The currently dominant Omicron variant 2019-nCoV has low pathogenicity but high transmissibility, unlike other variants. This has resulted in a global increase in the incidence of COVID-19 .This study was limited by the single-center base, resulting in a small number of participants. Therefore, additional multi-centered studies with an increased number of participants are required. Further, unvaccinated mothers and those who contracted 2019-nCoV in their 3rd trimester were enrolled in this study. A future analysis of 2019-nCoV infection by gestational weeks may be beneficial.


Regarding air pollutants, although the daily limits for PM10 were exceeded on less than 5% of days, the annual average overtook the values proposed by WHO. Thus, we concluded that prematurity and low birth weight in this region are related to air pollution, and to socioeconomic variables and health care.Brazil has one of the largest mineral coal reserves in the world. More than 40% of this ore is in the Candiota Mine, in the extreme south of Brazil, which was previously identified as a hotspot of environmental pollution. In addition, an important part of Brazil’s population suffers from socioeconomic vulnerability. Since there is no information on unfavorable gestational and neonatal outcomes associated with these problems, we conducted a cross-sectional study with 1950 mother–child binomials, aiming to evaluate the association between these outcomes and air pollution as well as socioeconomic, demographic and health variables in seven cities in the region. Of the total births, 11.6% were preterm and 9.5% of neonates had low birth weight (<2500 g). These conditions were also associated with skin color, previous abortions, birth type and prenatal care, as well as exposure to higher levels of coarse particulate matter (PM Coal is the most harmful energy source for the environment  because Developing countries have encouraged the policy of using coal for power generation based on increased demand for energy and the economic benefits generated . Brazil Coal exposure has several negative impacts on human health, especially in vulnerable groups such as pregnant women and children. Maternal exposure to ambient air pollution is a well-recognized risk factor for adverse neonatal and obstetric outcomes, due to the significant transplacental transfer of contaminants ,13,14. AThe public health impact of coal-based energy production on maternal and child health is a concern worldwide, especially considering the elevated cost to public health of environmentally mediated diseases . Coal poResearch in the study region has shown an environment with moderate levels of contaminants ,22, but n = 128), where a coal-fired power plant and two coal surface-mining operations are situated, and six neighboring municipalities—Aceguá , Bagé , Hulha Negra , Pedras Altas , Pinheiro Machado , and Herval   . These s10), sulfur dioxide (SO2), nitric oxide (NO) and nitrogen dioxide (NO2)—were extracted from automatic monitoring stations installed in three cities in the region: Candiota , Aceguá (city located west of Candiota) and Pedras Altas (city located east of Candiota).Data on air pollutants—coarse particulate matter  of all children born during the year of 2013 to mothers residing in the study area. DLB information was also collected in hospitals from two neighboring municipalities, where some of those mothers eventually gave birth to their children. The DLB is a tool whose objective is to provide important information on the characteristics of live births, together with data on the mother and pregnancy, throughout the Brazilian territory. This information was collected to adequately assess the evolution of maternal and newborn care and health based on statistical, sociodemographic and epidemiological data. Since it was implemented by the Ministry of Health, the government keeps the data and health professionals  are responsible for completing the DLB after the birth of the child.All ethical principles laid down by the National Health Council were respected, and the Ethics Committee in Health Research from the Universidade Federal do Rio Grande (CEPAS/FURG) approved this study under protocol nº 036/2013.Maternal, pregnancy and neonatal outcomes were collected, such as first month of prenatal care , prenatal care  and number of previous pregnancies and abortions. Pregnancy and birth outcomes included gestational age , 5th minute Apgar score ; birth weight ; and presence of congenital disorders .p-values, Poisson regression was performed with robust variance estimates, according to hierarchical levels ; 2nd Level—maternal housing; 3rd Level—reproductive history: previous fetal losses/abortions and pregnancies, birth type; 4th Level—prenatal care and birth conditions: prenatal consultations and initiation of prenatal care; 5th Level—birth type, gestational age). To avoid confounding factors, the variables that presented p ≤ 0.2 were maintained in the model until the end, even though they lost their significance with the introduction of other variables of a lower hierarchical level. In the unadjusted and adjusted analyses, only children born from single pregnancies were included (n = 1910), while in descriptive analysis all births were included (n = 1950). In all analyses, values were considered significant when p < 0.05.The data were double-digitized and checked into EPIINFO software, and the analysis was subsequently conducted using STATA 10.0. First, the prevalence of each variable and outcome was calculated. To estimate the crude and adjusted prevalence ratios and their respective confidence intervals (95%) as well as the 10 exceeded the Brazilian limits at the Candiota station and at the Aceguá station. The other pollutants did not have averages above the limits for annual averages. Even so, sporadic daily episodes exceeded the daily limits provided for in the legislation.Detailed information on the levels of air pollutants monitored in the region is described in This study evaluated 1950 births among the seven municipalities from the coal mining region. As shown in Most mothers began their prenatal care in the first semester (77.4%), and had adequate prenatal care (68.6%). The majority of newborns were born by cesarean (68.6%) and were boys. Despite the low prevalence of negative outcomes , 11.6% of newborns were preterm, 1.1% had 5th minute Apgar score of <6, 9.5% were of low birth weight and 68.3% of weight ≥3000 g at birth. Less than 1% had congenital disorders .Stratified analysis showed significant differences between the municipalities: Candiota had a high prevalence of births at <37 weeks 14.9%; . When st10 exposure was significantly associated with preterm birth only in the adjusted model. The other variables investigated did not show significant associations with preterm birth, including NO2 and SO2.10 in the first trimester was significantly associated with low birth weight only in the adjusted model. Low birth weight did not show associations with the other variables investigated, including NO2 and SO2.As shown in Several factors can determine maternal and child health, such as biological, social and environmental conditions. This study evaluated maternal and newborn outcomes among 1950 births from seven municipalities situated in the largest Brazilian coal mining region, in addition to evaluating the risk of preterm birth and low birth weight. This region has received special attention in environmental health ,31,32,33Environmental and social vulnerability renders the population more susceptible to environmental pollution ,36. MateAbortion is considered the most common and severe complication of pregnancy. In Brazil the incidence range is 13–28% . AbortioIn this study, a significant proportion of mothers had later initiation of prenatal care and an insufficient number of visits compared to other coal mining areas . PrenataThe prevalence of cesarean births in the study was much higher than that recommended by the WHO (10–15%). There are studies that show a high prevalence of C-sections in Brazil, and in the cities of Rio Grande do Sul State. Marmitt et al. , in theiThe prevalence of congenital disorders was similar to that of the Rio Grande do Sul State  and high10 concentrations  did not reach the level considered a public health problem . On theThe study has some limitations, as the data were collected from DLB forms, which can show errors in completion. Additionally, these forms do not contain lifestyle information such as smoking, alcohol consumption, maternal weight and family income, which are important predictors of maternal and neonatal outcomes. Furthermore, the cities studied had different numbers of records because many births were not in the city of residence of the mothers, due to the precarious health conditions.10 during the first trimester of pregnancy were associated with the outcomes studied. The sum of socioeconomic and environmental vulnerability in this population exposes it to the risks of unfavorable health outcomes.Of the total of 1950 annual births in the region, 11.6% were premature and 9.5% of newborns had low birth weight (<2500 g). Skin color, previous miscarriage, type of delivery and prenatal care were associated with these two outcomes (prematurity and low birth weight). In addition, higher levels of PM


This study aimed to develop and validate claims-based algorithms for identifying live birth, fetal death, and cesarean section by utilizing administrative data from a university hospital in Japan. We included women who visited the Department of Obstetrics at a university hospital in 2018. The diagnosis, medical procedures, and medication data were used to identify potential cases of live birth, fetal death, and cesarean section. By reviewing electronic medical records, we evaluated the positive predictive values (PPVs) and the accuracy of the end date of pregnancy for each claims datum. “Selected algorithm 1” based on PPVs and “selected algorithm 2” based on both the PPVs and the accuracy of the end date of pregnancy were developed. A total of 1757 women were included, and the mean age was 32.8 years. The PPVs of “selected algorithm 1” and “selected algorithm 2” were both 98.1% for live birth, 99.0% and 98.9% for fetal death, and 99.7% and 100.0% for cesarean section, respectively. These findings suggest that the developed algorithms are useful for future studies for evaluating live birth, fetal death, and cesarean section with an accurate end date of pregnancy. The age of women giving birth has been rising in Japan . Due to Utilizing the healthcare administrative database is one of the practical approaches to evaluating birth outcomes in real-world clinical settings and the information on rare treatment exposures ,11,12. VThe current study bridges this research gap. It aims to develop and validate algorithms to identify birth-related outcomes  and the accuracy of the end date of pregnancy by using healthcare claims data from the Tohoku University Hospital in Japan.We used electronic claims data at Tohoku University Hospital, containing diagnoses according to the International Classification of Diseases, 10th revision (ICD-10) codes, medical procedures , and medication. The study population included all women who visited the Department of Obstetrics at Tohoku University Hospital between January 2018 and December 2018. There were no exclusion criteria.We evaluated live birth, fetal death, and cesarean section. In this study, we classified fetal death as miscarriage (defined as spontaneous abortion ≤ 21 weeks gestation), stillbirth (defined as spontaneous abortion > 21 weeks gestation), and induced abortion. To identify potential cases in each outcome, we used the obstetric diagnosis without the “suspected” flag, medication, and medical procedure listed in We used electronic medical records (EMRs) as the gold standard to determine the accuracy of potential cases in each outcome. If a potential case had pregnancies several times in the study period based on EMR information, the accuracy was determined separately considering the date of the claim for each outcome. At Tohoku University Hospital, the Department of Obstetrics has developed and maintained a listing of EMR information regarding birth outcomes. We utilized the listing to review potential cases. However, since the listing only includes the birth outcomes of women who terminated their pregnancy after 12 weeks of gestation at Tohoku University, women who terminated their pregnancy before 12 weeks or those who delivered in other hospitals were not identified. Thus, if outcomes of potential cases were not available in the listing, the details of other unstructured data from EMRs were manually reviewed by three pharmacists. In the manual EMR review, two out of three pharmacists mutually reviewed the outcomes and the end date of pregnancy for each potential case. Any disagreements were resolved through discussion to obtain a final judgment by the third pharmacist.The age of the study population was calculated based on the first date of the claim entry and their birth date. However, if the women who visited the department of obstetrics at Tohoku University Hospital did not have any claims, their age at the time of their visit could not be identified directly. Therefore, we calculated the maternal age on 30 June 2018 because 30 June lies midway on the calendar.To evaluate how accurately each claim datum identifies birth-related outcomes, we descriptively summarized the cases identified by each claim data. If the final outcomes could not be judged even after the EMR review due to a hospital transfer, these cases were categorized as “unevaluable”.Additionally, we aimed to evaluate the accuracy of the date of the claim for birth-related outcomes. Regarding the end date of pregnancy in each birth-related outcome, we calculated the difference between the date of the claim data and that of the EMR. If one woman had multiple entries in the same claims data, we evaluated both the earliest date and the latest date and compared the results.For the subsequent analysis, we took “selected algorithm 1” and “selected algorithm 2” to evaluate the validity of birth-related outcomes and the accuracy of the end date of pregnancy; “selected algorithm 1” was developed by combining the claims data (based on an “or” condition), of which positive predictive values (PPVs) were 80% or higher. PPVs were defined as the proportion of true-positive cases divided by the claims-positive cases. As a conservative approach for developing “selected algorithm 1”, we regarded “unevaluable” as a false positive instead of removing it from the dataset to avoid overestimating the accuracy. For exploratory analysis, we assessed the additional algorithms by subtracting those who had the claims codes of “selected algorithm 1” for fetal death from those who had inaccurate claims codes (with the PPVs under 80%) for live birth to evaluate whether the accuracy for live birth would improve.From the “selected algorithm 1”, we developed a “selected algorithm 2” by strictly selecting the claims data with an accurate end date of pregnancy. We considered the date of the claim to be accurate if the percentage that met the criteria (the difference between the date of claim and the true end date of pregnancy was within ±7 days) was 80% or higher. For “selected algorithm 1” and “selected algorithm 2”, PPVs and corresponding 95% confidence intervals (CI) were also estimated.All analyses were performed using SAS version 9.4 .This study included 1757 women who visited the Department of Obstetrics at Tohoku University Hospital in 2018. Of them, 29 (1.7%) were 15–19 years old, 448 (25.5%) were 20–29 years old, 1089 (62.0%) were 30–39 years old, 186 (10.6%) were 40–49 years old, and 5 (0.3%) were over 50 years old. The mean age was 32.8 (standard deviation: 5.9) years.n = 731), cesarean section (complexity fee addition) , and cesarean section (elective cesarean section)  were often observed for live birth (n = 35), missed abortion , and dilatation and curettage (missed abortion)  were common in fetal death (n = 262), cesarean section (elective cesarean section) , and cesarean section (emergency cesarean section)  were common in cesarean sections (n = 1).Each claim entry and its name, the number of subjects, and the difference between the date of administrative data and EMRs for birth-related outcomes are summarized in ve birth . Additioal death , while csections . It is wFor exploratory analysis, we subtracted those who had the claims data for fetal death from those who had the claims data with PPVs under 80% for live birth. The PPVs of live birth were 0.0% (O711), 79.2% (O720), 50.0% (O723), 76.2% , 81.2% , and 0.0 % (gemeprost suppository), and no women were identified for J8001.The date was generally accurate regarding all medical procedures with a PPV of 80% or higher for live birth, fetal death, and cesarean section. Considering the date difference between claims data and the end date of pregnancy in EMRs, the percentages that fell within the range of ±7 days were almost 100.0%, although K90920 (dilatation and curettage (missed abortion)) was 96.3%. However, regarding some claims of diagnosis, the percentages that fell within the range of ±7 days were under 80.0% for live birth  in The PPVs of “selected algorithms 1” and “selected algorithms 2” were both 98.1% (95% CI 96.9–98.9%) for live birth, 99.0% (95% CI 94.4–100.0%) and 98.9% (95% CI 94.2–100.0%) for fetal death, and 99.7% (95% CI 98.4–100.0%) and 100.0% (95% CI 98.9–100.0%) for cesarean section, respectively . Every aFor fetal death outcomes, only two cases resulted in stillbirth; thus, the table focusing on stillbirth has not been displayed. Miscarriage and induced abortion are summarized in To the best of our knowledge, this is the first study to develop and evaluate the validity of algorithms to identify live birth, fetal death, including miscarriage and induced abortion, and cesarean section using administrative data in Japan.The value of the current study lies in providing information on the accuracy of multiple birth-related outcomes based on claims information in Japan. In Western countries, various validation studies identifying live birth, miscarriage, stillbirth, induced abortion, and cesarean section have been reported and have demonstrated accuracy ,29,30,31In the current study, we developed an accurate algorithm for each birth-related outcome as “selected algorithm 1” by selecting the claims data with PPVs of 80% or higher. Combining the claims data could capture a larger number of potential outcomes than using the single claims data alone. Most of our investigated claims data related to fetal death and cesarean section represented accurate outcomes. However, some data  resulted in inaccuracy for live birth and were not incorporated into “selected algorithm 1”. Considering this result, we assessed additional algorithms in the exploratory analysis by subtracting those who had the claims data of “selected algorithm 1” for fetal death from those who had these inaccurate claims data for live birth. Overall, although the PPV of methylergometrine maleate tablets was over 80% in this exploratory analysis, there was no remarkable improvement in the accuracy of live birth. Considering these exploratory results and the complexity of the algorithms, these claims codes might not be utilized for future studies to identify live births. Notably, the number of codes  was very limited. Although preterm birth is an important adverse birth outcome, it might be difficult to identify it using the ICD-10 code in Japan. To identify preterm birth, the use of algorithms for the onset of pregnancy , as wellFollowing the assessment of “selected algorithm 1”, we also assessed the accuracy of the end date of pregnancy; “selected algorithm 2” was identified as an accurate algorithm for both the outcome and its date. Considering the accuracy of the date, the medical procedure codes and the claims data by using the latest date were accurate in general, which was consistent with previous reports . We recoOur study had some limitations. First, since the current study was conducted in a single university hospital in Japan, our results may not be generalizable to other medical institutions, including general clinics. The population in this study likely included older women, who may be at risk during pregnancy and delivery. Furthermore, the number of fetal deaths and cesarean sections might be larger in university hospitals than in general clinics. Although the system for medical fee processing was standardized and the government provided the master files under the healthcare system in Japan, further studies may be required to determine whether our results could be extrapolated to other hospitals. Second, we were unable to review the negative cases of the algorithm due to the study’s resources. Thus, the sensitivity, specificity, and negative predictive value were not assessed. We believe that our results provide useful information, especially for future comparative studies, to evaluate the relative risk of birth-related outcomes between exposure and control. Third, regarding birth-related outcomes, we assessed outcomes for women who had transferred to another hospital as “unevaluable”. However, as a conservative approach, we defined the selected algorithms in the current study by regarding “unevaluable” as false positives instead of removing them from the dataset to avoid overestimating the accuracy. Lastly, we could not evaluate some claims data related to birth-related outcomes because some specific codes were not observed in the administrative claims during our study period. For example, our study did not cover some of the ICD-10 codes of “O00-O99 Pregnancy, childbirth, and the puerperium”. Therefore, the accuracy of non-evaluated claims data was uncertain. Furthermore, given that some claims data were based on only a few potential cases in this study, results with these uncommon claims data should be carefully interpreted. Therefore, future studies with these non-evaluated and uncommon claims data in our study are suggested.We developed reliable combination algorithms to identify live birth, fetal death, and cesarean section based on the evaluation of the accuracy of each claim data, as well as the accuracy of the date of claim. Since validated claims-based algorithms with information on the PPVs and the accuracy of the dates are required to provide a certain level of credibility for the research use of claims data, we recommend utilizing our validated algorithms for each birth-related outcome. Our findings will benefit future studies that attempt to evaluate birth-related outcomes in real-world clinical settings.


Women's satisfaction with their childbirth experiences has significant impacts on their health and the health of their children. Recently, childbirth and maternity care systems have been disrupted by the COVID-19 pandemic. This study aimed to investigate the association of birth satisfaction with mode of birth, medical interventions, support during labour, type of childbirth healthcare plan and antenatal education in the context of the COVID-19 pandemic in Russia.1,645 Russian women who gave birth during the first year of the COVID-19 pandemic and 611 matched controls who gave birth in the previous year participated in an anonymous Internet survey about their childbirth experience. The survey included questions regarding women's demographic and obstetric characteristics as well as their childbirth experiences. Birth satisfaction was measured using the Birth Satisfaction Scale Revised Indicator (BSS-RI).p = 0.22). Women had lower BSS-RI scores if they tested positive for COVID-19 during labour , but not during pregnancy or postpartum (p > 0.32). In both cohorts women who had vaginal births rated birth satisfaction higher than those who had caesarean births. The more medical interventions there were, the lower were the BSS-RI scores , but only during the pandemic. Birth satisfaction was higher if women had a support person present during labour , which was not possible for over 70% of participants during the pandemic. In both cohorts birth satisfaction was associated with the childbirth healthcare plan , but not with antenatal education .Birth satisfaction scores did not show notable changes before and during the pandemic (Pearson Chi-square = 19.7, Our study highlights the significant impacts of the COVID-19 pandemic on the birth experiences of Russian women. Sustaining the rights of women to informed decisions during labour, respect for their preferred childbirth healthcare plan, presence of the birth team of choice and professional support for home birth are essential for higher birth satisfaction and better health outcomes for mothers and their infants. A negative birth experience is associated with higher rates of postpartum depression , posttraSadly, worldwide reproductive health services have conventionally focused their efforts and resources on reducing perinatal mortality and have paid less attention to the psychological aspects of women's childbirth experiences , 11. HowBirth satisfaction has been linked to various obstetric, sociodemographic, and psychological factors , 15. By The association between women's levels of satisfaction with their birth experiences and the use of epidural analgesia is also debated. In a Swedish study Ulfsdottir and colleagues found the use of epidural analgesia to be a risk factor for a negative childbirth experience . This fiWhile obstetric factors are most studied in relation to birth experience, in her systematic review, Ellen Hodnett indicates that overall, biomedical interventions did not affect women's experiences of childbirth as much as the attitudes and behaviours of the healthcare providers . Indeed,via association with more biomedicalised birth and greater incongruence with women's birth plan  and matched controls who gave birth one year prior (January 2019–February 2020). Finally, we examined whether birth satisfaction was associated with having COVID-19 diagnosis before, during or after delivery.2.2.1.via perinatal education classes and specialised online and offline communities for new parents. 611 mothers of infants aged 0–13 months (M = 6.37) participated in the study before the pandemic, and 1,645 mothers of infants aged 0–13 months (M = 6.93) completed the online survey during the pandemic. All respondents provided informed consent to participate in the study. The inclusion criteria were respondent's age of 18 years and over, ability to read and write in Russian, and having given birth to a live-born child no longer than 14 months prior to the study.During the period from January to February 2020 and February to March 2021 women were invited to take part in the study 2.2.2.2.1.The survey for both cohorts included questions regarding the participants' age at the time of childbirth, education , place of childbirth , and marital status (married/cohabiting with partner/single). Information about the type of the childbirth healthcare plan was collected . Respondents also provided information regarding obstetric characteristics such as parity, gestational age at birth, time since birth, and mode of birth .The participants were also asked to report whether there were any biomedical interventions during labour and what type of interventions were administered .Further information about the sources of support during labour was collected (none/partner/doula or private midwife/partner + doula or private midwife) and antenatal education type .The survey also included questions about the COVID-19 diagnosis: whether the respondents themselves or any of their family members were diagnosed with COVID-19 during pregnancy, at the moment of delivery or postpartum.2.2.2.α = 0.805).We used the Birth Satisfaction Scale Revised Indicator (BSS-RI)  to asses2.2.3.All the analyses were controlled for maternal age at the time of childbirth, level of education, family status, time after childbirth, gestational age, parity and place of childbirth.2.3.Spearman's correlation coefficient was used to estimate the relationship between BSS-RI scores and the covariates.We explored the association between the BSS-RI scores and birth experience factors  using generalised linear models.Multiple linear regression analysis examined the association between BSSR-RI scores and age at testing, gestational age and parity.Pearson Chi-square tests were performed to compare the demographic and birth experience characteristics between the first cohort (before the pandemic) and the follow-up (during the pandemic).All analyses were performed using IBM SPSS 25 software .3.Demographic, obstetric and childbirth characteristics for participants from the two stages of the study before and during the COVID-19 pandemic are presented in p = 0.22).Birth satisfaction scores did not show notable changes before and during the pandemic  and negatively with age . During the pandemic there was no correlation with age, while the association with parity remained statistically significant . Furthermore, in the follow-up study birth satisfaction scores were correlated with gestational age at birth , with no such association before the pandemic . Contrarily, there was a significant association between the place of birth and BSS-RI scores before the pandemic , but not during the pandemic . There were no significant associations with other covariates either before or during the pandemic .Among the covariates before the pandemic birth satisfaction positively correlated with parity (3.1.p < 0.001). There were fewer emergency CBs  and more planned CBs  during the pandemic in comparison to pre-pandemic times. Furthermore, the frequency of assisted vaginal births also decreased significantly during the pandemic .During the pandemic the frequencies of different modes of birth have changed  and during the pandemic . After adjustment for covariates there was a significant association between BSS-RI scores and mode of birth both before , while there was a slight decrease in the use of synthetic oxytocin during the pandemic . The more biomedical interventions there were, the lower were the BSS-RI scores . However, this effect was notable only during the pandemic, with no such association before the pandemic . The frequency of biomedical interventions during labour virtually remained the same before and during the pandemic . Table 13.2.p < 0.001). p < 0.001).During the pandemic, labour support has changed significantly  and during the pandemic . After adjustment for covariates, birth satisfaction was significantly associated with the mode of support during labour both before (3.3.p = 0.020).F = 5.27, p < 0.001) and during the pandemic . Women who gave birth at home had the highest mean BSS-RI scores in both cohorts . via self-education during the pandemic in comparison to 37% of women before the pandemic . The number of participants with a mixed type of antenatal education also increased .During the pandemic the types of antenatal education changed significantly  or during the pandemic .After adjustment for covariates there was no association between BSS-RI scores and the antenatal education type before , but not during pregnancy or the postpartum period .After adjustment for covariates, having a confirmed COVID-19 diagnosis was associated with lower BSS-RI scores, if tested positive in the hospital during labour , in comparison to pre-pandemic period . HoweverThe evidence on biomedical interventions during the pandemic is contradictory. Verhoeven and colleagues report a decrease in episiotomy use during the pandemic, but an increase in the use of epidural analgesia use . The datSupport during labour has been consistently linked with better birth experiences –24, 57 aAntenatal education is widely popular in Russia, and the majority of women tend to prepare for childbirth, using various strategies . In our One more possible explanation of these findings is the variety of antenatal education courses. In this study we did not investigate the contents of different birth preparation courses, yet these could vary tremendously from hospital-based classes to traditional “women circles”, providing evidence-based information or ethnoscience . The typ5.Strengths of our study include the substantial sample sizes of the two cohorts, use of validated psychometric tools, and thorough investigation of birth experiences. Moreover, the inclusion of the questions regarding the COVID-19 diagnosis before, during and after childbirth allows us to evaluate its prevalence and direct effect on women's birth satisfaction. However, several limitations should be addressed when interpreting our results. First, the data for both cohorts was collected anonymously and exclusively online, which may impact the reliability of the responses. Second, all the data are based on self-reports, with no medical records or other objective information on the participants' health and obstetric history, which may limit its validity. Another limitation that should be considered is the unidimensional nature of the BSS-RI measurement of birth satisfaction . It pres6.Taken together, the results from this study shed light on how the measures that were introduced to protect women, their children, and healthcare workers against the spread of COVID-19 infection had a significant impact on birth experience and birth satisfaction in Russian women. Particularly, lack of respect for the preferred type of childbirth healthcare plan, mode of birth, and amount of medical procedures, as well as lack of support during labour were associated with notably lower birth satisfaction. Thus, these findings provide further support for current 2018 WHO guidelines for intrapartum care  on the i


To investigate transfer strategies in the frozen-thawed embryo transfer (FET) cycle.n = 558), high-quality plus poor-quality double blastocyst group , poor-quality double blastocyst group , high-quality double blastocyst group , and poor-quality single blastocyst group . Inter-group comparison analyses of primary conditions, pregnancy outcomes and neonatal outcomes were then performed.The clinical data of 1,652 FET patients were divided into five groups according to the number and quality of the transferred blastocyst: high-quality single blastocyst group  and high-quality blastocyst transfer  were found to be protective factors for live birth. In addition, double blastocyst transfer was also the largest risk factor for pregnancy complications  and neonatal complications , especially for gemellary pregnancy  and preterm birth . Based on the ROC curves, a double blastocyst transfer could predict gemellary pregnancy reliably with a high area under the curve (AUC = 78.53%). Additionally, a double blastocyst transfer could effectively predict a high risk of pregnancy complications (AUC = 65.90%), neonatal complications (AUC = 64.80%) and preterm birth (AUC = 66.20%).Group A had the highest embryo implantation rate (67.38%), significantly different from the implantation rates of the other four groups. The gemellary pregnancy rate (1.60%), preterm birth rate (5.58%), neonatal birth weight , neonatal birth age , and incidence of low birth weight (7.02%) in group A were different from those in groups B, C, and D, but did not significantly differ from those in group E. Moreover, the proportions of male infants born in groups A (56.86%) and D (59.41%) were significantly higher than those in the other three groups. Double blastocyst transfer (0.528, 95% CI [0.410–0.680], The live birth rate of frozen-thawed high-quality single blastocyst transfer is lower than that of double high-quality blastocyst transfer, which can significantly increase the embryo implantation rate. High-quality single blastocyst transfer also significantly lowers the risk of gemellary pregnancy, preterm birth, and low birth weight, and can significantly improve maternal and infant outcomes. After weighing the pros and cons of live birth with pregnancy and neonatal complications, the authors believe that high-quality single blastocyst transfer is the optimal FET strategy for young women and is worthy of further clinical application. Despite this recommendation, high-quality single blastocyst transfer can increase the risk of monozygotic twins, as well as significantly increase the proportion of male infants born. Assisted reproductive technology (ART) has been around for over 40 years. The blastocyst culture and transfer technique is a widely used technique that improves the pregnancy outcomes of ART . As blasIn 2009, the British Human Fertilization and Embryology Society (HFEA) issued a policy requiring the routine application of SET in reproductive centers. Since then, the ART gemellary pregnancy rate in the UK has dropped from 26.6% in 2008 to 16.3% in 2013, and the overall live birth rate with ART has not been affected . Over thThis study retrospectively analyzed the clinical data of 1,652 patients who received FET in the reproductive center of the Second Affiliated Hospital of Wenzhou Medical University from January 2019 to December 2020 and analyzed the pregnancy and neonatal outcomes of five FET strategies. The conclusions of this study can help provide a reference for the optimal FET strategy for treating infertility in young women.A retrospective analysis of females undergoing FET was performed from January 2019 to December 2020 in the reproductive center of the Second Affiliated Hospital of Wenzhou Medical University. The inclusion criteria were as follows: (1) all patients were between the ages of 20 and 35 years old, and the causes of infertility included tubal obstruction, endometriosis (EMs), polycystic ovary syndrome (PCOS), male factors, or unexplained reasons; (2) the endometrial layer thickness was greater than seven mm on the day of endometrial transformation; (3) patients had no more than two transplant cycles; (4) single or double Day 5 (D5) blastocysts were transferred; (5) hormone replacement therapy was used for endometrial preparation. The exclusion criteria were as follows: (1) Uterine abnormality under ultrasound such as endometrial polyps, endometrial fibroids, intrauterine adhesion or uterine malformation; (2) malignant tumor or other systemic diseases; (3) congenital genetic abnormalities; (4) genital tract malformations; (5) history of recurrent miscarriage; (6) Day 6/7 (D6/7) blastocyst or Day 3/4 (D3/4) cleavage stage embryo transferred; (7) the use of other endometrial preparation programs, such as daily natural therapy, ovulation induction therapy, and gonadotrophin releasing hormone analogue (GnRH-a) down-regulating hormone replacement therapy.n = 558), high-quality plus poor-quality double blastocyst group , poor-quality double blastocyst group , high-quality double blastocyst group , and poor-quality single blastocyst group  of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University and informed written consent was obtained from all participants (2021-K-74-02).HRT patients commenced oral administration of one tablet of estradiol  twice a day on the 2nd-5th day of the menstrual cycle. A B-ultrasound was performed every 3 to 5 days to measure the endometrial thickness and adjust the estradiol dosage accordingly. When the endometrial thickness ≥8 mm and serum progesterone levels <1.5 ng/ml, patients were given 10 mg dydrogesterone tablets , in addition to the one tablet of estradiol, orally twice a day and 200 mg micronized progesterone was also administered orally or vaginally twice a day . Single or double blastocysts for embryo transfer were selected on the 5th day after the endometrial transfer. The methods used for luteal phase support were the same as those used after endometrial transformation .On the morning of transplantation, the blastocysts were thawed using a vitrification recovery kit . The carrier rod was removed from the liquid nitrogen, and then the casing was taken out and quickly placed in the thawing solution (TS) at room temperature for 1 min. The blastocysts were then transferred into the diluent (DS) for 3 min, washing solution 1 (WS1) for 5 min, washing solution 2 (WS2) for 5 min, and finally transferred to a pre-prepared petri dish, washed three times and left to culture until transplantation.After the blastocysts were thawed, they were graded according to the Gardner classification system , which iβ-hCG test was performed on day 12 of the FET cycle. The first B-ultrasound was performed after the 26th day of the FET cycle and the second B-ultrasound was on day 40 , and intrahepatic cholestasis (ICP). Neonatal complications included: preterm birth, low birth weight, birth defect, and macrosomia.t-test, Pearson’s chi-square test or Mann–Whitney U test, and the Fisher’s exact test as appropriate. Multivariate logistic regression was used to analyze major factors affecting live birth, pregnancy complications and neonatal complications, and odds ratios (ORs) and 95% confidence intervals for independent variables were calculated. Receiver operating characteristic (ROC) curves were used to assess whether double embryo transfer and high-quality blastocyst transfer could be used to accurately predict live birth, pregnancy complications, gemellary pregnancy, neonatal complications, and preterm birth. All analyses were two-tailed and difference of P < 0.05 was considered as statistically significant. All data were analyzed using SPSS  in this study.Continuous variables are presented as the mean and standard deviation or median, and the comparison between the five groups was performed using one-way analysis of variance. In contrast, data not conforming to normal distribution was presented as medians and interquartile ranges (IQRs), and five comparisons between groups were performed using the Kruskal-Wallis H test. Clinical variables were compared using independent P > 0.05). Group A was statistically different from group C in the amount of infertility cases that were caused by male factors  or that were unexplained . Both factors in group D were statistically different from group A  and group C . The proportion of patients in the first transplant cycle was highest in group A, which was significantly different from the other four groups , and the proportion of patients in the first cycle was the lowest in group C, which was significantly different from group D  and group E . The rate of positive hCG tests  and the clinical pregnancy rate  in group E were significantly lower than those of the other four groups. Group A had the highest embryo implantation rate, which significantly differed from the other four groups . The gemellary pregnancy rate  and the preterm birth rate  were the lowest in group A compared to groups B, C, and D, there was no statistical difference between group A and group E (P > 0.05). The biochemical pregnancy rate in group A (9.14%) was significantly different from groups C  and E . Group D had the highest live birth rate (62.75%), which differed significantly from group A , group C , and group E . In group A, neonatal birth weight was significantly higher , neonatal birth age was significantly higher , and the incidence of low birth weight infants was significantly lower  than groups B, C, and D . The incidence of macrosomia in group E (15.63%) was significantly higher than in group B , group C , and group D , but did not significantly differ from group A. The proportions of male infants born in groups A (56.85%) was significantly higher than the proportions of male infants born in groups B, C, and E . The proportions of male infants born in groups D (59.41%) was significantly higher than the proportions of male infants born in groups B, C, and E  or a non-live birth group (n = 768) according to whether the ART led to live birth. In univariable analysis, the main factors associated with live birth were infertility duration, BMI, transplant cycle, number of embryos transferred, high-quality blastocyst transfer, and poor-quality blastocyst transfer.The 1,652 patients included in this study were divided into a live birth group , 24 ≤BMI<28  and being on the second transplant cycle . Double blastocyst transfer  and high-quality blastocyst transfer  were found to be protective factors for live birth  were divided into two groups according to the occurrence of pregnancy complications. In univariable analysis, the main factors associated with pregnancy complications were BMI, transplant cycle, number of embryos transferred, high-quality blastocyst transfer, poor-quality blastocyst transfer, and endometrial thickness.Females with serum hCG ≥15 mlU/mL , double blastocyst transfer , and endometrial thickness >12 mm  and double blastocyst transfer. Poor-quality blastocyst transfer  was protective against gemellary pregnancy  were divided into two groups based on the presence or absence of neonatal complications. In univariable analysis, the main factors associated with neonatal complications were infertility duration, BMI, maternal age, transplant cycle, number of embryos transferred, poor-quality blastocyst transfer, and endometriosis.All live births , 18.5 ≤BMI<24 , 24 ≤BMI<28 , BMI>28 , double blastocyst transfer , and endometriosis , double blastocyst transfer , and endometriosis  and P value <0.001. In addition, double blastocyst transfer was correlated with live birth , pregnancy complications , neonatal complications , and preterm birth  and To improve pregnancy outcomes, conventional ART techniques often adopt double blastocyst transfer, increasing the risk of gemellary pregnancy. Gemellary pregnancy is high risk and can seriously threaten the health of both the mother and the baby. Embryo number is significantly correlated with pregnancy outcomes. Embryo reduction and reducing the number of embryos transferred both stop gemellary pregnancy. However, embryo reduction is a remedial measure, while reducing the number of embryos transferred is a preventive measure. Studies have shown that a frozen-thawed single blastocyst transfer can effectively prevent gemellary pregnancy and reduce pregnancy and neonatal complications . HoweverIn order to investigate the effect of the number and quality of transferred blastocysts in FET on pregnancy outcomes and to formulate the optimal FET strategy for blastocyst transfer, patients undergoing frozen-thawed blastocyst transfer were divided into five groups according to the number and quality of the transferred blastocysts. The results showed that group A had a clinical pregnancy rate similar to other groups (except for group E), without increasing the risk of adverse pregnancies such as miscarriage, biochemical pregnancy, ectopic pregnancy, and other obstetric-related complications. Although the live birth rate in group D was higher than in group A, the gemellary pregnancy rate and preterm birth rate in groups B, C, and D, were significantly higher than in group A. By conducting a multi-factor logistic regression analysis, we found that double blastocyst transfer  and high-quality blastocyst transfer  were protective factors for live birth, but double blastocyst transfer was also a risk factor for pregnancy complications  and neonatal complications . For example, double blastocyst transfer was associated with a nearly 60-fold increase in the probability of gemellary pregnancy  and a 3.84-fold increase in the incidence of preterm birth  compared to single blastocyst transfer. According to a recent meta-analysis , for youvs. 52.5%; Embryo implantation rate refers to the ratio of implanted embryos to transferred embryos. In frozen-thawed blastocyst transfer, the implantation rate of elective DET is significantly lower than that of SET . In this study, six cases of MZT occurred in group A (an incidence of 1.6%) and one MZT occurred in group E (an incidence of 2.2%). Some research indicates that blastocyst transfers can increase the rate of MZT by 4.25 times compared with natural pregnancy (1.7% Neonatal outcomes also differed between the groups. Group A had significantly higher birth weights and gestational ages than the three double blastocyst transfer groups. Group A also had the lowest incidence of low birth weight, and group D had the lowest incidence of macrosomia. Group A had the lowest incidence of low birth weight because that double blastocyst transfer significantly increased the gemellary pregnancy rate. Gemellary pregnancy has significant risks including increased morbidity of newborns, premature delivery, low birth weight, and very low birth weight . The aimThis study has three major limitations, which we expect will be solved in future studies. First, our study population only included young women and excluded women of advanced age, so it needs to be double blastocyst transferermined whether frozen-thawed high-quality single blastocyst transfer is also suitable for women of advanced age. Second, we only investigated the pregnancy outcomes of FET fertility treatments. No analysis was done on the cumulative pregnancy rate, and the intellectual and physical development of the newborns after birth was not tracked. Finally, this was a single-center retrospective study. Large, prospective, multi-centered, randomized controlled trials that strictly control for exogenous variables are required to confirm the advantages of high-quality single blastocyst transfers in the FET cycle for treating infertility.High-quality single blastocyst transfers in the FET cycle have a high live birth rate and implantation rate, significantly lower gemellary pregnancy rate, and lower rates of premature or low birth weight infants. Maternal and infant outcomes are also significantly improved with this method. According to a multiple-factor analysis, double blastocyst transfer and high-quality blastocyst transfer were protective factors for live birth. However, double blastocyst transfer was also a risk factor for pregnancy and neonatal complications. After weighing the pros and cons of live birth with pregnancy and neonatal complications, we conclude that high-quality single blastocyst transfer remains the optimal FET strategy, but it should be noted that high-quality single blastocyst transfer does not entirely remove the risk of gemellary pregnancy, so the possibility of MZT should be considered. This study even included a DC-DA case, which contradicts the current understanding of gemellary pregnancy progression and is worthy of further confirmation. In addition, the proportion of males born from high-quality single blastocyst transfer was notably higher than in other transfer techniques. This possible impact should be considered in future studies. This study is of great clinical significance for blastocyst selection in the FET cycle and the effective reduction of ART gemellary pregnancy rate.10.7717/peerj.14424/supp-1Supplemental Information 1Click here for additional data file.


Introduction: The aim of this study was to investigate associations between death and sociodemographic and clinical determinants in a neonatal ICU (NICU) in Athens, Greece, by means of a case-control study.Methods: The study was conducted between January 2013 and October 2017 at the NICU of “Panayiotis & Aglaia Kyriakou” Children’s Hospital in Athens, Greece. The NICU subjects that died (case group) during this period (n=49) were compared with a control group of 451 NICU-admitted subjects who survived, during the same period. Potential determinants of mortality were assessed; univariate and multivariate logistic regression analysis was performed; odds ratios (OR) and 95% confidence intervals (95% CIs) were estimated.Results: Gestational age less than 32 weeks , low birth weight , emergency transfer , cyanosis , perinatal asphyxia , necrotizing enterocolitis , need for oxygen supply, and incubator use emerged as independent predictors of mortality.Conclusion: Extreme prematurity, low birth weight, necrotizing enterocolitis, and emergency conditions are associated with mortality, despite progress made in the field of neonatal intensive care. Infant mortality is a major public health issue worldwide. The infant mortality rate, defined as the annual number of infant deaths in a country's population per 1000 live births, is a metric that reflects the overall quality of health services and the socioeconomic level of the population in a country and is particularly used by public health agents and policymakers. Neonatal mortality is the major contributor to infant mortality, accounting for 70-80% of deaths in the first year of life [Globally, about 4 million children die each year before the completion of the first year of life. In recent decades, a remarkable decline in infant mortality has been achieved, from 65 deaths per 1,000 live births in 1990 to 29 infant deaths per 1,000 live births in 2018 -5.In developed countries, the main risk factors affecting infant mortality are preterm birth, low birth weight, and congenital malformations, whereas infections, birth asphyxia, injuries, maternal pregnancy complications, and sudden infant death syndrome account for the remainder of infant deaths .The infant mortality rate in Greece is at low levels; however, the declining trends in the first decade of the 21st century have stagnated over the last decade due to the negative impact of the recent economic crisis in the country . MoreoveIn a small number of published studies, some researchers have attempted to present the recent trends of infant mortality in the Greek population; however, there is a gap in the literature regarding the epidemiological profile of neonatal and infant mortality in the country ,12. The This study was conducted in the NICU of the “Panayiotis & Aglaia Kyriakou” Children’s Hospital in Athens, Greece, which is one of the two pediatric hospitals in the city. The study has been approved by the local Institutional Ethics Committee. A case-control design was implemented among the infants hospitalized during the January 2013 - October 2017 period in the hospital. The case group consisted of all infants who died (n=49), whereas the control group consisted of 451 infants who were hospitalized in the NICU and survived. All data were retrospectively reviewed.The following parameters were abstracted from the hospital archives: gender, gestational age at birth , birth weight , multiple pregnancy, birthplace (Athens or outside Athens), hospital of birth (private or public), method of transfer to the Unit (by the parents or by emergency), cyanosis, gestational diabetes, gestational hypertension, maternal substance use, maternal hepatitis B (HBV) status, chorioamnionitis, neonatal jaundice, perinatal asphyxia, respiratory distress syndrome, necrotizing enterocolitis, and use of oxygen supply and use of incubator during hospitalization.Categorical variables were expressed as absolute and relative frequencies and were compared using chi-squared or Fisher’s exact test, as appropriate. Univariate and multivariate logistic regression analysis was performed. The case-control status was set as the dependent variable; the determinants were set as the independent variables and odds ratios (OR) with 95% confidence intervals (95% CI) were estimated. A core model including extreme/very preterm birth  and low birth weight (<2500 vs. ≥ 2500 g) was the basis of the multivariate analysis. At the multivariate analysis, the effects of determinants proven significant at the univariate analysis were adjusted for the aforementioned two variables (extreme/very preterm birth and low birth weight) of the core model. The level of statistical significance was set at 0.05. Statistical analysis was performed with Stata/SE version 16.1 software .Descriptive statistics of the case-control study are shown in Table The majority of subjects in the case group were born before 32 weeks , whereas the majority of subjects in the control group  pertained to full-term births (≥37 weeks); gestational age was associated with infant death (p<0.001). Low birth weight was more frequent in the case group . Emergency transfer to the Unit , cyanosis , chorioamnionitis , perinatal asphyxia , respiratory distress syndrome , necrotizing enterocolitis , oxygen supply  and incubator use  were associated with death status. On the other hand, gender (p=0.282), multiple pregnancy (p=0.249), birthplace (p=0.316), public or private hospital of birth (p=0.092), gestational diabetes (p=0.496), gestational hypertension (p>0.999), maternal substance use (p=0.463), maternal HBV status (p=0.433), neonatal jaundice (p=0.295) were not associated with death status.The results of univariate and multivariate logistic regression analysis are shown in Table At the core model encompassing mutual adjustment between extreme/very preterm birth and low birth weight status, both variables were significantly associated with infant death , cyanosis , perinatal asphyxia , necrotizing enterocolitis , need for oxygen supply  and incubator use  were positively associated with infant death.On the other hand, chorioamnionitis  and respiratory distress syndrome  lost their significance in the multivariate analysis adjusting for prematurity and low birth weight.This case-control study highlighted the independent associations of predictors of death in the context of a NICU. Extreme/very preterm birth, low birth weight, emergency transfer to the unit, cyanosis, perinatal asphyxia and necrotizing enterocolitis, need for oxygen supply, and incubator use emerged as independent predictors of infant mortality, with sizeable effect estimates.Low birth weight and prematurity are well-established risk factors of severity in the NICU setting; neonatal disease severity scores have included those factors in the core variable set. A systematic review published in 2017 summarizing model parameters of prognostic models for predicting in-hospital neonatal mortality recorded the presence of gestational age and birth weight in SNAP  models . AfterwaThis case-control study showed independent associations between neonatal death and necrotizing enterocolitis. The latter has been acknowledged as a major cause of morbidity and mortality in the NICU; a recent systematic review and meta-analysis showed an incidence of the condition equal to 7% of all very low birth-weight infants . PretermCyanosis, perinatal asphyxia, and the need for oxygen supply reflect the respiratory status of the infant; various respiratory status parameters have been a consistent part of scoring systems for the prediction of neonatal mortality . From a health system- and public health policy-related point of view, the emergency transfer to the unit seems of special interest as a predictor of mortality. A qualitative study conducted in neonatologists documented the concerns of the specialists vis-à-vis neonatal transfers, including the need for the readiness of paramedics to undertake the transfers, the need for soundness in the referral processes, and coordination between hospital staff, paramedics, and members of the transport team . The par Various limitations of this study should be declared. First, associations with potentially meaningful predictors of mortality, such as chorioamnionitis and respiratory distress syndrome did not reach significance; larger samples may well be needed for the documentation of these effects. In addition, the study recruitment period was prior to the COVID-19 pandemic; therefore, any differential effects of the mortality predictors during the COVID-19 era could not be addressed. More elaborate indices, such as small-for-gestation age, or composite severity scores were not available for inclusion in the analysis of the study. Moreover, additional, detailed clinical indices, such as body temperature, pH, blood pressure, oxygen saturation, hypoglycemia, and the presence of seizures, were not available for this study. Preterm birth, low birth weight, emergency transfer to the unit, cyanosis, perinatal asphyxia, necrotizing enterocolitis, need for oxygen supply, and incubator use emerged as independent predictors of mortality in the context of a neonatal intensive care unit. Further longitudinal cohort studies, adjusting for composite scores and addressing any potential added value of the aforementioned set of variables are warranted.


The Thornwald cyst is a congenital cyst in the region of the pharyngeal bursa, formed by a communication between the notochord and the nasopharyngeal endoderm. It has an incidence of 3% in the adult population. Most cases are diagnosed during the second and third decades of life, with higher prevalence in malesPatients are usually asymptomatic, and they may present symptoms such as nasal obstruction, foreign body sensation, hearing loss, periodic halitosis with an unpleasant taste and nasopharyngeal dischargeSince it is a benign lesion, asymptomatic cysts do not require treatment. Symptomatic cases can be operated by endonasal or transoral approach. Marsupialization is the procedure of choice to avoid recurrencesFemale patient, 43 years old, had had constant and progressive nasal obstruction for the past 3 years, that worsened when laying down, accompanied by foreign body sensation in the posterior nasal region, postnasal dripping, halitosis, nasal itching and sneezing.Fiber optic nasal-laryngoscopy showed a yellowish cystic lesion with a smooth surface covered with mucosa in the posterosuperior nasopharynx, obstructing approximately 60% of its lumen. Computed tomography of the paranasal sinuses  revealedAfter detailed physical examination and imaging studies, we hypothesized the patient had a Thornwaldt cyst.® (power 4.0 Watts) diode laser. We vaporized the anterior capsule of the cyst linearly and vertically, aspirated its contents (cytology) and removed small wall fragments (histology). After that, we progressively vaporized both free edges of the cyst in the lateral direction  or transpalatine approach for larger cysts. It can be performed by the cold approach or use of electrocautery, which decreases the chance of bleeding; however, it uses high temperatures, damaging healthy tissues that permeate the cystWe chose to use the diode laser, which is characterized by a small diameter fiber, flexible and easy to handle. The method allows for endonasal treatment, which ensures good visualization of the lesion and surrounding structures, making the procedure safer and efficientThe area of thermal necrosis is only 0.5 mm, resulting in little injury to adjacent tissues, improving healing and reducing postoperative pain. It provides adequate hemostasis and control of tissue binding, facilitating the procedure and reducing its complications.The main disadvantage of using laser is its high costThe use of the diode laser to treat the Thornwaldt cyst proved, in our case, to be a safe and easy-to-perform procedure, with good postoperative results, making it a possible alternative for the treatment of these lesions.


Preterm newborn infants are characterized by low body weight and lower fat mass at birth compared with full-term newborn neonates. Conversely, at term corrected age, body fat mass is more represented in preterm newborn infants, causing a predisposition to developing metabolic syndrome and cardiovascular diseases in later life with a different risk profile in men as compared with women. Postnatal growth is a complex change in anthropometric parameters and body composition. Both quantity and quality of growth are regulated by several factors such as fetal programming, early nutrition, and gut microbiota. Weight gain alone is not an optimal indicator of nutritional status as it does not accurately describe weight quality. The analysis of body composition represents a potentially useful tool to predict later metabolic and cardiovascular risk as it detects the quality of growth by differentiating between fat and lean mass. Longitudinal follow-up of preterm newborn infants could take advantage of body composition analysis in order to identify high-risk patients who apply early preventive strategies. This narrative review aimed to examine the state-of-the-art body composition among born preterm children, with a focus on those in the pre-school age group. Preterm birth (PB) may seriously affect postnatal growth and neurodevelopment and increase the risk of adverse outcomes from infancy to adulthood. Yearly, 15 million babies in the world are born before 37 weeks of gestation; in Europe, the estimated rate of PB ranges from 5 to 10% (Although at birth preterm infants are characterized by a lower weight and fat mass (FM), at term corrected age, their body fat percentage is more represented if compared with full-term infants. This peculiar pattern of growth that occurs during the first weeks of life is a consequence of complex metabolic and endocrine adaptations at extrauterine life and is also affected by early nutrition. The enhanced importance of early life nutrition and optimization of growth in terms of body composition is mainly related to the advances in neonatal intensive care, which allow the survival of infants of lower gestational age. Indeed, rapid catch-up growth during infancy and childhood is related to an increased risk of developing non-communicable diseases, including cardiovascular diseases and metabolic syndrome in later life .The study of body composition (BC) and growth patterns during early life allows us to better understand the longitudinal associations among body compartments, metabolic–endocrine pathways, and health consequences in the long term .This review aimed to investigate the state-of-the-art scientific literature regarding BC analysis among preterm born children, focusing on pre-school age. To better understand how BC can predict metabolic risk in later phases of life, we examined the role of key factors related to BC, such as fetal programming, early nutrition, and gut microbiota.Due to the wide heterogeneity across studies in terms of populations , terminologies , and methodologies in measuring BC (2 or more compartments model-based), we provide a narrative review to avoid inappropriate comparisons of heterogeneous data.Prematurity refers to a birth that occurs before 37 weeks of pregnancy . AccordiPB is characterized by Low Birth Weight . Particularly, preterm infants could be categorized according to BW as Very Low Birth Weight , Extremely Low Birth Weight , and Micro Preemie (BW < 750 g). There are few concepts and definitions that may overlap and should be clarified when approaching PB. Small for Gestational Age (SGA) refers to the birthweight below the 10th percentile of recommended sex-specific birth weight for the referenced GA (Intrauterine growth restriction (IUGR) is an abnormal fetal growth pattern referring to an impoverished fetal growth due to fetal, maternal, or placental factors . IUGR reSeveral studies suggest that metabolic and cardiovascular risk originates during intrauterine life and it is related to the programming of cardiovascular and metabolic functions . The proBarker hypothesized that small size at birth has a causal relationship with the development of hypertension, coronary heart disease, and non-insulin-dependent diabetes, in middle age. LBW infants considered in his study were mainly SGA and IUGR because the mortality rate of premature newborn infants was very high at that time  [Barker1Initially attributed solely to SGA and IUGR infants, the phenomenon of FP has subsequently been expanded to include preterm infants . The matThe consequences of PB on angiogenesis and kidney development are among the most studied. PB leads to an interruption in angiogenesis, which causes altered patterns of development of the vascular tree that is apparent as early as infancy. Data from long-term follow-up studies have shown an inverse relationship between gestational age and risk of adult hypertension in both men and women who were born preterm . AlteratRegarding the impact of PB on kidney development, an important aspect is nephron endowment which is the number of nephrons that an individual has at birth. In the human fetus, nephrogenesis reaches completion at 34–36 weeks of gestation with more than 60% of nephrons being formed in the last trimester; therefore, nephron endowment is low in infants born preterm. In 1997, Brenner proposed the hyperfiltration theory, which hypothesized that early loss of nephrons mass results in hyperfiltration of remaining nephrons, proteinuria, progressive kidney injury, and increased risk of hypertension in later life . PretermMultifactorial diseases such as diabetes or hypertension are the result of complex interactions between genetic constitution and environmental factors that act from the fetal age to determine the adult phenotype. In the attempt to clarify the mechanisms of fetal programming, there is an emerging interest in the role of epigenetic modifications. Epigenetic changes can permanently modify gene expression without altering DNA sequence, are established in early development, and, once set, are mitotically heritable . EpigeneHospitalized preterm newborn infants require intensive care management  and frequently experience elevated oxidative stress and inflammation. Oxidative stress occurs when there is an imbalance between reactive oxygen species (ROS) and antioxidant systems and may contribute to significant pathology in the maternal–infant dyad. The downstream inflammation and cellular damage that results from oxidative stress have implications on the developing kidneys, lungs, and cardiovascular system. In immature newborns, exposure to supplemental oxygen may halt microvessel growth in the lung and retina, leading to serious short−term complications such as bronchopulmonary dysplasia and retinopathy of prematurity. In the developing kidney, the negative impact of oxidative stress related to fluctuating oxygen exposure from hyperoxia to intermittent hypoxia has also been implicated in the development of kidney injury in postnatal animal models . There iThe aim of nutritional care in preterm infants is to promote a postnatal gain of weight which should follow the growth trajectory they would have in the womb, aiming to avoid growth failure and neurodevelopment delay , 22. Of LBW has been often used as an index of inadequate fetal growth to predict the subsequent risk of comorbidities. Not only does BW influence the risk of non-communicable disease but as pointed out by Lucas et al. it plays an important role in the changes in size between birth and adulthood, which have a deeper impact on disease development than birth weight alone .Anthropometry consists of height, weight, head circumference, body circumferences, and skinfold thickness. It is considered an applicable, inexpensive, and non-invasive method to study measurements and proportions of the human body . AnthropWeight, which is the sum of several different compartments , is the key parameter for assessing growth velocity. The two methods most frequently used are grams per kilogram per day according to Patel’s exponential model (EM), which uses weights from 2-time points  and FentHowever, when body weight modifies, a standard scale does not detect which tissue and how much changes. Therefore, the weight alone does not accurately reflect the neonatal quality of growth. Moreover, considering the high hydration rate of infants, weight is strongly affected by fluid status . In addiBC is the best long-term indicator of nutritional status both in the state of health and disease . Wang etBC assessment in preterm infants is challenging as growth patterns are not linear. Furthermore, PB can alter the pattern of adiposity, with an increased risk of developing metabolic diseases . For thiStudies measuring preterm body composition are mostly performed when infants reach term equivalent age (TEA), referred to as the 40th week of gestation. At TEA, preterm infants have been shown to have decreased amounts of FFM and increased FM% when compared with term infants of the same GA .Several methods allow us to measure the different tissues or compartments. Currently, most studies use air displacement plethysmography (ADP) and dual-energy x-ray absorptiometry (DXA), while only a few studies have applied MRI and ultrasound imaging (US).Unfortunately, due to the wide heterogeneity across methodologies and assumptions, body composition values collected using different methods cannot be compared . Moreove2 (p = 0.53) (p = 0.34)  . Measure = 0.53)  and are  = 0.53) . Moreove = 0.34) . However = 0.34) , 49, 50.DXA is based on the emission of low- and high-energy x-rays toward each point of the body pixel and then evaluates the x-ray attenuation as they pass through the tissues. It is a quick, reliable, and repeatable method and provides information about regional FM, non-bone lean mass, and bone mineral content and density, according to a three-compartment model. However, it has some critical issues. It exposes subjects to a small quantity of radiation, it may overestimate body fat, and it requires both expensive machines and specifically skilled investigators. ADP and DXA provide data on fat mass, which is different from adipose tissue , 52; in MRI is a four-compartment technique. It estimates the volume of adipose tissue and gives information about lean body mass, water, and bone mass either per body area or in the whole body. It is considered a reliable method for the evaluation of subcutaneous and visceral fat. MRI technique quantifies adipose tissue volume as voxels or volume elements. MRI detects both adipose tissue depots and ectopic fat in the liver and skeletal muscle . It is aUS is another emerging technique used to measure regional lean tissues and FM according to the two-compartment model . The US Organ growth and development begin soon after conception when the fetus is composed only of FFM. FM accumulation occurs later in pregnancy, with the aim of enhancing the chance of survival of newborns after the interruption of maternal supply at birth . After bFrom the embryonic stage, human tissues can synthesize lipids using glucose which contributes to increasing the fetal adipose tissue. During early pregnancy, insulin resistance and estrogen effects increase maternal fat depots and adipose tissue breakdown with subsequent hypertriglyceridemia. All fatty acids (FAs) can provide energy by mitochondrial fatty acid oxidation pathway, but polyunsaturated fatty acids of the n-3 or n-6 series are the preferential substrate essential for structural and metabolic intrauterine development. Most FAs from the maternal circulation are esterified and associated with lipoproteins, which are taken up by the placenta and hydrolyzed by lipases. Fetal fat accretion during the last weeks of gestation occurs very rapidly and is sustained by FAs crossing the placenta and fetal lipogenesis .Development of adipose tissue begins during the second trimester of intrauterine life and it is a dynamic process, continuing lifelong. This process involves both mechanisms of hypertrophy (size enlargement of adipocyte cells) and hyperplasia (increases in the number of adipocytes within a lobule). At 14 weeks of gestation, the first fat depots can be detected, and the primitive fat lobules develop. The number of lobules increases until about 23 weeks GA. Successively, until 29 weeks GA, adipose tissue grows as fat lobule size increases, which continues throughout postnatal life, while the fat lobule number remains constant. During the last 10 weeks of gestation, fat mass increases linearly with GA, especially in subcutaneous adipose tissue . It has Overall, in full-term infants, FM growth is linear with the increase in fat cell size during the first months of life, whereas the number of fat cells remains stable. Conversely, PB alters the ideal growth pattern and disrupts the ontogeny development of BC; in addition, preterm infants experience a difficult absorption of fatty acids due to the immaturity of the gastrointestinal tract .in utero , mean FM% was 8.3 ± 4.1 and FFM 1.88 ± 0.4 kg . Giannì in utero of full-term newborns, predisposing to metabolic syndrome and cardiovascular disease in childhood and adulthood. The meta-analysis of Johnson et al. showed that, at TEA, preterm infants have greater FM measured with ADP by 6.3%  compared with full-term infants  (p = 0.594), differently from FFM values   at TEA, as compared with term neonates  . In a Dup < 0.001) at TEA in comparison with full-term newborns at birth (p < 0.001) at TEA compared with full term  compared to full term  at TEA were lighter and shorter than term newborns, and with higher FM% and lower FFM by ADP measurements. At 5 years, compared with term, both male and female preterm infants remained significantly lighter  and shorter ; males presented higher FM% (20.4 ± 5.0 vs. 17.9 ± 5.5) and lower FFM  and full-term children resolve in preschool age, with infancy FFM gains associated with preschool lean mass and prematurity not associated with FM evaluated at 4 years of age in both sexes . It shouMihatsch et al. demonstrated that VLBW infants (mean GA at birth 29 ± 3 weeks) at 3 years have less FM% (19 ± 4 vs. 22 ± 4) and FFM in grams than full-term infants , without evidence of increased truncal fat in preterm infants evaluated by DXA  are lighter and shorter and both early preterm girls and boys express less FM% than full-term infants by ADP measurement . Similarly, less FFM in kilograms both in early preterm girls and boys compared to the full-term was noticed . Moreover, GA was correlated with anthropometry and BC only in premature girls .The growth pattern is affected by GA. Ibáñez et al. showed that SGA infants have a peculiar catch-up growth compared with appropriate GA infants, characterized by shorter size and higher central adiposity according to DXA values at 2–4 years . The groFetal, rather than postnatal, FFM tissue accretion was associated with developmental progression . Moreovep < 0.001), while the males have higher mean FFM as well as higher birth weight  and with fat mass development in females (to support elevated energy requirements during pregnancy and lactation) . In facth weight .Males and females respond differently to the intrauterine environment. The placenta’s ability to transport nutrients from mother to fetus, reflected in its size, allows optimal fetal growth. Male fetal growth is more rapid and invests in brain growth rather than placental growth. Consequently, there is a greater risk of undernutrition that may lead to LBW and, in the long-term, vulnerability to cardiovascular disorders .p < 0.001) at 6 weeks of postnatal age, using ADP to measure BC. Authors have hypothesized this is due to a lesser accretion in lean body mass in the first few weeks of extrauterine life  have a significantly higher percentage of body fat than those full term  . Expressp < 0.01) and lower FM%  compared with those fed with formula  at TEA, while VLBW infants fed with a formula developed higher fat mass evaluated by bioelectrical impedance analysis as compared with full term   .The growth in preterm infants fed with HM is characterized by a preferential FFM deposition which, unlike fat gain, seems to contribute to the improvement of neurodevelopment outcomes , 87.As previously discussed, the disadvantage in male preterm is multifactorial and boys require higher nutritional intake compared to girls to support optimal linear growth and BC . There iBifidobacterium and Lactobacillus. In contrast, the microbiome of formula-fed infants presents a relative abundance of Bacteroidetes and Firmicutes with increased Clostridium difficile  and Enterococcaceae  and limited microbial diversity . In theincreased . The micoccaceae , 120, distridium .Streptococcus at 2 days of age and Bacteroides group at 10 days of age were found to affect weight gain at 1 month of age (Staphylococcus, Clostridium, and Enterococcus have been associated with an increased ratio between carbohydrates and total caloric intake, reflecting a potential change in the energy balance and an increased growth due to a greater expression of genes involved in lipid and carbohydrate metabolism (As PB alters gut microbiota development, an association among gut microbiota composition, nutrition, and infant growth has been suggested. The levels of Enterobacteriaceae and h of age . Grier etabolism .Nevertheless, Stewart et al. showed that at 1–3 years, the preterm gut microbiome has a complexity comparable to healthy term infants regardless of antibiotic use and the presence of diseases. They supposed that introducing semisolid foods can promote the development and diversification of gut microbiota into the adult form . The gutPB disrupts the metabolic and endocrine maternal–placental unit. Preterm newborn infants are characterized by low body weight and lower fat mass than full-term born because of the interrupted supply of nutrients during intrauterine fetal growth. The postnatal adaptation to extrauterine life leads to the accretion of fat mass, aiming to improve thermoregulation and increase body energy stores. Therefore, at term equivalent age, body fat percentage is more represented in preterm as compared with full-term born neonates, causing a predisposition to developing metabolic syndrome and cardiovascular diseases in childhood and adulthood.Both quantity and quality of growth are regulated by several factors such as fetal programming, early nutrition, and gut microbiota. Moreover, the differences in body composition have been reported between males and females born preterm in a not consistent way across the studies; the mechanisms are likely to be multifactorial including the differential activity of the placenta and endocrine activation in response to stress. As gain in weight alone is not an optimal indicator of nutritional status, analysis of body composition represents a potentially useful tool to predict later metabolic and cardiovascular risk allowing detection of the quality of growth by differentiating between fat and lean mass through longitudinal measurements.Body composition analysis provides the missing key to optimally manage preterm neonates. Indeed, the study of body compartments may reveal a “dys-phenotype” that predisposes to later metabolic risk, even during the first phases of life.AC: conceptualization and writing the original draft. AC and AS: methodology. AC, AS, MP, GV, FS, and EM: data curation. FS, RC, and MS: supervision. All authors have supervised and contributed to the writing, review, and editing of the final version of this manuscript.