To assess the association between chromosomal polymorphisms (CPM) with congenital anomalies and perinatal complications in a cohort of newborns from couples undergoing intracytoplasmic sperm injection (ICSI), trophectoderm biopsy, and preimplantation genetic testing for aneuploidy (PGT-A).A retrospective cohort of singletons conceived after ICSI, trophectoderm biopsy, and PGT-A cycles performed at IVIRMA clinics in Spain over 4 years was involved in the study. Newborns were classified according to the parental karyotype analysis: Group I: non-carriers, Group II: CPM carriers. Couples with chromosomal anomalies and instances when both partners were CPM carriers were excluded from the study. The groups were compared for several perinatal complications.p = 0.0406). There were no statistical differences among the two groups regarding congenital anomalies, preterm birth, alterations in birth length and weight, cranial perimeter, Apgar test score, or sex ratio (p > 0.05).There was a significant decrease in the number of NB with complications in the carrier group compared to the non-carriers (19.7% vs 31.9%, Chromosomal polymorphisms appear to have no adverse effects on congenital anomalies or perinatal complications on newborns from ICSI + PGT-A cycles. Infertility is a significant condition worldwide, affecting up to 10–15% of all couples of reproductive ages. In 2018, the International Committee for Monitoring Assisted Reproductive Technologies – ICMART – reported that an estimated eight million infants were born worldwide from Assisted Reproductive Technologies (ART) in the last 40 years [Some studies performed on national registries in the United States, Australia, Denmark, Finland, Norway, and Sweden have found a higher incidence of congenital defects in ART infants compared to those conceived spontaneously –4. The sIt is well known that genetic anomalies are an important cause of human infertility –9. CytogIn recent years, several groups have investigated the prevalence of CPM in different ethnic infertile populations. Most of these studies have reported that the incidence is three to five times higher in the infertile population compared to the fertile population, indicating that CPM may have an impact on infertility –13. CPMsThe effects of CPM on ART are contradictory. Some studies found no effect of these variants on ART outcomes , whereasGiven the possible effect that CPMs have on reproduction, the objective of this study was to determine the association between these variants and pregnancy outcomes after infertility treatment, especially the effect they have on congenital abnormalities and perinatal complications.A retrospective analysis was carried out on a cohort of newborns (NB) from infertile couples. All couples underwent ICSI + PGT-A treatments where the embryo transfer was performed between January 2015 and December 2018, at IVIRMA Global clinics located in Spain. They had one or two euploid embryos transferred and had a singleton pregnancy, with a live NB. All couples underwent karyotype screening before treatment. Exclusion criteria included couples with abnormal karyotypes, multiple pregnancies, gamete donation, cleavage stage biopsy, and females with an anatomical defect of the reproductive system. Data were anonymized and extracted from the digital platform for clinical information management of IVIRMA Global.NBs were grouped according to parental karyotype analysis: Group I (control group) included 1,253 NBs with normal chromosome parents; Group II included 66 NBs with CPM carrier parents . NBs from couples with polymorphic variants of chromosomes in both males and females were excluded from the study. This study was approved by the Institutional Review Board at IVIRMA Global and by the Spanish Clinical Research Ethics Committee.Chromosome analysis was centralized in a reference cytogenetic laboratory , performed by culture of peripheral blood lymphocytes stimulated with phytohemagglutinin and subsequent staining with trypsin-Giemsa (GTG bands). A total of 15 metaphases were evaluated for each of the subjects and the banding resolution was 400–550 bands per haploid set. Polymorphisms were included only when their size was greater or smaller than at least twice the size of the corresponding region on the homolog chromosome . HeteromAn increase or decrease in the length of the heterochromatin on the long arm of chromosomes 1/9/16/Y were designated as qh + or qh-. An increase or decrease in lengths of the stalks on the short arm of the acrocentric chromosomes (D/G groups) was recorded as 13/14/15/21/22 pstk ± . Double and increased satellites on the short arm on the same chromosomal group could also be observed and were designated as pss and ps + . An increase in lengths of heterochromatin region on the centromere was recorded as cenh + . The pericentric inversions of chromosome 9 were also considered chromosomal polymorphism. Multiple variations consisted of more than one variant.Patients underwent ovarian stimulation using standardized protocols based on age, antral follicle count (AFC), antimullerian hormone (AMH), and body mass index (BMI). When 3 or more follicles reached 18 mm in diameter, ovulation trigger was performed with r-hCG  or GnRH analog . Intracytoplasmic sperm injection was performed in all cases, and fertilization was assessed 16–18 h after microinjection. Embryos were cultured using a sequential culture system  .On day 3, all embryos were subjected to laser-assisted hatching, and on days 5–6, all non-arrested embryos underwent laser-assisted trophectoderm biopsy. All blastocysts were individually vitrified within 1–2 h after biopsy using Kitazato vitrification kit (Kitazato Biopharma) until PGT + A results were available. Chromosomal analysis was centralized in a reference genetic laboratory (Igenomix), using Array Comparative Genomic Hybridization (aCGH) or Next-generation sequencing (NGS) technologies , 24.After testing, euploid embryos were thawed using a commercially available warming solution (Kitazato Biopharma) following the manufacturer’s instructions and then cultured for 2–6 h. Thawing of the blastocysts was prioritized based on the best quality before biopsy, and only blastocysts that re-expanded after warming were considered suitable for transfer.No more than two embryos were transferred in all cycles, with single embryo transfer always recommended. Approximately two weeks after embryo transfer, blood levels of hCG were tested. Clinical pregnancy was then confirmed via ultrasound with the presence of a gestational sac and a fetal heartbeat at 6 weeks after embryo transfer. Obstetric control was conducted outside of IVIRMA facilities.According to the routine follow-up process at IVIRMA Global, all clinically pregnant patients were contacted after at least one month of the expected due date to confirm their pregnancy outcomes and complete the follow-up chart. This included perinatal complications, date of birth, birth weight, birth height, sex of the babies, neonatal diseases, cranial perimeter, and birth defects. Preterm birth (PB) was defined as birth before 37 weeks of gestation, very preterm birth (VPB) was defined as birth before 32 weeks of gestation, and post-term birth was defined as birth during or after 42 weeks of gestation. Low birth weight (LBW) was defined as < 2,500 g, very low birth weight (VLBW) was defined as < 1,500 g, and high birth weight (HBW) was defined as weight over 4,000 g.Congenital malformations and perinatal complications presented by NBs were categorized following the 10th edition of the International Classification of Diseases (ICD-10), chapter XVII for congenital malformations, deformations, and chromosomal abnormalities, and chapter XVI for conditions originating in the perinatal period, which includes pathologies that have their origin before birth and up to the first 28 days after delivery, even if the morbidity occurs later.p < 0.05 was considered statistically significant. As this is a retrospective study, there was no actual sample size calculation. According to the patient selection criteria and the number of records included in the database, a description was made of the statistical power that was possible to achieve with the available data. Considering the selection criteria and the study period, we believed to have more than enough statistical power to find clinically relevant differences that could be statistically confirmed.Continuous data were compared using Mann–Whitney U test, and the results are presented as the Median (interquartile range). Categorical data are presented as percentages, and Fisher’s exact test was used for comparisons. All statistical analyses were conducted using Statistical Package for GraphPad Prism version 9.1.2, and A total of 1,319 live singletons were included in this study, 66 of them from CPM carriers couples . The incidence of chromosomal polymorphism variations in infertile couples was 5.0% (2.2% for men and 2.8% for women). The distribution of chromosomes with CPM was different between genders . Furthermore, we analyzed the male and female carriers separately. The AFC was significantly decreased in the female carriers (8.0 (6.5 – 12.0), p = 0,0138) but not in the partners of the male carriers (11.0 (6.5 – 18.3), p = 0,7484), compared to the non-carriers (data not shown). There were no significant differences between the days of stimulation, FSH or HMG dose, estradiol (E2), and progesterone (P4) levels on hCG day, the number of oocytes retrieved or the number of oocytes MII (p > 0.05).The basal data of the two groups were compared, and statistical analysis showed no differences for maternal age, BMI, years of infertility, or female basal AMH, (p > 0.05). When analyzing male and female carriers separately, male partners of female carriers had similar sperm parameters to the control group (p > 0.05), while men carriers had lower sperm quality, though the difference was not significant (p > 0.05) (data not shown).Sperm parameters are shown in Table p = 0.0429). When analyzing male and female carries separately, female carriers had similar fertilization rate to the control group (75.0 (61.5 – 86.0) vs 78.0 (65.0 – 88.0), p = 0.3494), but for male carriers, fertilization rate was significant decrease (73.0 (53.0 – 81.0), p = 0.0417). Regarding the number of good quality blastocyst per cycle, blastocyst formation rate, abnormal blastocyst rate and proportion of SET/DET, there were no statistical differences between groups (p > 0.05).IVF outcomes are shown in Table p = 0.0406). Furthermore, when analyzing male and female carriers separately, female carriers had significantly lower NB complications than the control group , but not male carriers . There were no differences between groups in Apgar test score at minutes 1 and 5, length and weight at birth, cranial perimeter, frequency of C-section, sex ratio, frequency of birth weight alterations, or duration of pregnancy.Perinatal outcomes for each group are presented in Table p > 0.9999), but male carriers presented the highest frequency . sRegarding congenital anomalies, there were no statistical differences between the groups. Interestingly, there were no congenital anomalies for female carriers , which means that we cannot rule out a possible impact of CPM on congenital anomalies on babies conceived after ICSI- + PGT-A. Based on these limitations, further studies in similar settings and with a higher number of individuals are needed to confirm our findings.In summary, parental chromosomal polymorphisms do not appear to have a significant negative effect on congenital malformation development and perinatal complications when euploid embryos are transferred in ICSI + PGT-A cycles. Future studies, however, should evaluate the effect these variants have on pregnancy outcomes after infertility treatment when PGT-A is not performed.


What are the main findings?Restricted prenatal growth is associated with increased higher-order aberrations in adulthood.There was an association between increased higher-order aberrations correlating with lower visual acuity and spherical equivalent.What is the implication of the main finding?These results indicate that corneal development is influenced by fetal growth irrespective of prematurity, leading to life-long alterations of ocular shape.Increased corneal aberrations caused by adverse fetal growth might be a risk factor for reduced optical image quality in later life.®) to compare the corneal thickness and aberrations between adults classified as small for gestational age (SGA), normal birth weight (BW), and large for gestational age (LGA). Multivariable linear regression was applied to analyze associations with gestational age, BW percentile, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 448 eyes of 261 individuals born full term  were examined, including 29 severe SGA (BW < 3rd percentile), 32 moderate SGA (BW between 3rd and <10th percentile), 132 normal BW (BW between 10th and 90th percentile), 35 moderate LGA (BW between >90th and 97th percentile), and 33 severe LGA (BW > 97th percentile). There were no differences between groups in the corneal aberrations of the total cornea as well as of the corneal front surface, except for higher-order aberrations in the front of the cornea (p = 0.032). There was an association between the increased total root mean square of higher-order aberrations and lower birth weight percentile (p = 0.004), with increased higher-order aberrations correlating with lower visual acuity and spherical equivalent. Conclusion: Restricted prenatal growth is associated with increased higher-order aberrations in adulthood. Background/Aims: This study investigated whether there are changes in corneal surface regularity and corneal thickness in adults born small, appropriate, or large for gestational age at term. Methods: This retrospective cohort study involved prospective Scheimpflug imaging of the cornea (Pentacam A low birth weight due to preterm birth influences corneal geometry in childhood ,2, adoleInfants born small (SGA) and large for gestational age (LGA) are defined as having abnormal birth weight in relation to gestational age (GA). Moderate LGA is defined as a birth weight larger than the 90th percentile and severe LGA as larger than the 97th percentile, while moderate SGA is defined as a birth weight less than the 10th percentile and severe SGA as less than the 3rd percentile . OverallRecent analyses of preterm children have reported an inverse correlation between birth weight and corneal thickness ,11. The Hence, this study evaluated the long-term effects of being born severely or moderately SGA or LGA in adults born at term with respect to corneal aberrations, corneal thickness, and keratoconus indices.The present investigation is part of the Gutenberg Prematurity Eye Study (GPES), a single-center retrospective cohort study at the University Medical Center of the Johannes Gutenberg University Mainz in Germany (UMCM). The GPES involved a prospective ophthalmologic examination in adulthood and recruited individuals (i) born preterm or at term between 1969 and 2002 and (ii) between 18 and 52 years of age at study enrolment.n = 40), moderate SGA , AGA , moderate LGA , and severe LGA . Scheimpflug imaging of the participants was conducted between 2019 and 2021. In addition, all participants completed a questionnaire, and their relevant medical birth records were reviewed.All study participants were born at the UMCM between 1969 and 2002 with a gestational age ≥37 weeks. For each calendar month (from 1969 to 2002), six randomly selected full-term subjects  with a birth weight between the 10th and 90th percentile were invited and examined. The control group (group 3) of subjects born AGA (10th–90th percentile) in the present study was identical to the control group of the Gutenberg Prematurity Eye Study. Furthermore, for the present study, former term newborns of the UMCM were invited by age matching according to their birth weight percentile (40 participants in each birth weight percentile category group) and classified into severe SGA , Good Epidemiological Practice (GEP), and the ethical principles of the Declaration of Helsinki. The study protocol and study documents were approved by the local ethics committee of the Medical Chamber of Rhineland–Palatinate, Germany .Medical birth records were assessed, including pre-, peri-, and postnatal history .2−2 and Z22), vertical and horizontal coma (Z3−1 and Z31), vertical and horizontal trefoil (Z3−3 and Z33), spherical aberration (Z40), and root mean square of higher-order aberrations  and lower-order aberrations (RMS LOA). Lower-order aberrations included 1st and 2nd order aberrations . Corneal aberrations were computed for the total cornea as well as for the front and back of the corneal surface. In the case of decentration or low quality, the Scheimpflug measurement of that participant was excluded. A board-certified ophthalmologist reviewed each scan. Furthermore, the graphical distribution of corneal parameters was analyzed and skewness was calculated, with approximate normal distribution being assumed for skewness ≤ |1|. Signs of keratoconus were assessed by two board-certified ophthalmologists.Imaging of the anterior eye was performed with a Pentacam HR rotating Scheimpflug camera. To avoid examiner-dependent variance, all measurements were conducted according to standardized operating procedures. The Scheimpflug camera captures 25 images of the anterior segment within two seconds using an optical zone of 6 mm. A refractive index of 1.3375 was used to calculate the measurements of the anterior surface. The following corneal aberrations of the anterior and posterior surface of the cornea were recorded: oblique and vertical astigmatism  (D0); and circles around the thinnest corneal position with 2 (D2), 4 (D4), 6 (D6), 8 (D8), and 10 (D10) mm diameter. Distance-corrected visual acuity and objective refraction were evaluated in all participants .The covariables that may have affected the main outcome measures included sex , age (years), gestational age (weeks), birth weight (kg), birth weight percentile, placental insufficiency (yes), preeclampsia (yes), and breastfeeding (yes).Only participants with valid corneal tomography were included in the present analysis. Participants with measurements being judged as invalid or of low quality were excluded as were those with a history of corneal refractive, cataract surgery, or ocular trauma as this may have contributed to altered corneal shape.2−2 and Z22), corneal vertical and horizontal coma (Z3−1 and Z31), corneal vertical and horizontal trefoil (Z3−3 and Z33), corneal spherical aberrations (Z40), different keratoconus indices, and corneal thickness in circles around the cornea minimum.The primary outcomes were total corneal RMS HOA and LOA as well as central corneal thickness. The secondary outcomes were oblique and vertical astigmatism  was used to assess associations and to account for correlations between both eyes of one subject. In model #1, univariable analysis of the main outcome measures and GA (weeks), birth weight (kg), birth weight percentile, placental insufficiency (yes), preeclampsia (yes), and breastfeeding (yes) were computed. In model #2, associations with age (years), sex , GA (weeks), birth weight percentile (categories), placental insufficiency (yes), preeclampsia (yes), and breastfeeding (yes) were assessed in a multivariable model. Additionally, Spearman’s rank correlation was used to assess the correlation of total corneal aberrations and visual acuity and spherical equivalent. An additional sensitivity analysis was performed with the exclusion of participants wearing contact lenses. As this was an explorative study, a significance level was not defined, and no correction for multiple testing was carried out. Thus, the p-values are reported for descriptive purposes and should be interpreted with caution; findings with a p-value of <0.05 are discussed as potential differences. Calculations were performed using commercial statistical software .The descriptive statistics stratified by clinical group were computed for the main outcome measures. Absolute and relative frequencies were calculated for dichotomous parameters. Mean and standard deviation were calculated for approximately normally distributed data or median and interquartile range otherwise. Normally distributed ocular parameters of the different groups were compared with ANOVA and Kruskal–Wallis test if they were not normally distributed, and global This study involved 448 eyes of 261 individuals born at term , including 29 subjects with BW <3rd percentile, 32 with BW between 3rd and <10th percentile, 132 with BW between 10th and 90th percentile, 35 with BW between >90th and 97th percentile, and 33 with BW >97th percentile. The participant characteristics are shown in p = 0.032) (p = 0.022) and RMS LOA (p = 0.024)  . There w= 0.024) .p = 0.023) as well as spherical equivalent .Spearman’s rank correlation revealed an association between total corneal aberrations and distant corrected visual acuity  and birth weight percentile . Furthermore, birth weight and birth weight percentile were associated with higher-order aberrations in the univariable model (p = 0.004) but no associations between selected perinatal factors for lower-order aberrations  investigated 226 children born preterm and 259 children born full term at the age of 4 to 10 years. The results showed that preterm children had increased higher-order aberrations irrespective of the postnatal presence of ROP . In addiThe pathophysiological origins leading to these changes are still unclear, but there is evidence that corneal shape alterations persist until adulthood . While FSome other parameters have been described in the literature as having an impact on higher-order aberrations. Hashemi et al. evaluated higher-order aberrations in an adult population that included 904 eyes of 577 people and reported an association between higher-order aberrations and older age and shorter axial length, with fewer higher-order aberrations observed in emmetropes and the most higher-order aberrations observed in hyperopes . As therIn contrast to corneal aberrations, there were no associations between keratoconus indices and corneal thickness in subjects born at term. Our data are in contrast to the investigation of Pan et al. , which rOverall, corneal aberrations are an important factor for retinal image quality, and some authors have speculated that they are a decisive factor in the process of emmetropization , althougThe present study has several limitations. It is a single-center study and the optical quality of the eye, such as ocular wavefront analysis, was not investigated, so it was not possible to determine whether the increase in corneal higher-order aberrations leads to decreased image quality. Furthermore, the exclusion of participants with previous corneal refractive surgery can lead to a study bias, although none of the participants had previous corneal transplantation or corneal cross-linking. Nonetheless, the strength of the study is the inclusion of only subjects born at term stratified according to birth weight percentiles to investigate the effect of low and high birth weight in a relatively homogeneous group according to gestational age.The present study shows that altered fetal growth is associated with changes in higher- and lower-order aberrations of the cornea, indicating that corneal development is influenced by fetal growth irrespective of prematurity, leading to life-long alterations of ocular shape and potentially affecting visual function and refractive error.


Recently, the concern with birth interval has acquired importance in public health and family planning because of its implication for fertility, maternal, and child health. A short birth interval is associated with adverse perinatal, maternal, and infant outcomes. Moreover, too short birth interval lead to high fertility, which in turn contributes to accelerated population growth and undermines development efforts. This study aimed to investigate the prevalence of short birth interval and its associated factors among multiparous women in the Mieso agro-pastoralist district, Oromia region, Eastern Ethiopia.P-value of < 0.05.A community-based cross-sectional study was conducted from 1 to 30 March 2020. The multistage sampling technique was used to select 490 multiparous women. Data were collected by face-to-face interviewer-administered structured questionnaires. Bivariate and multivariable logistic regression analyses were executed. Model fitness and multicollinearity were checked. Statistically significant associations of outcome and independent variables were declared at a P-value <0.05.The prevalence of short birth interval was 56% (95% CI: 51.4–60.5) in the study area. Being married under 18 years , having formal education , having a husband with formal education , having awareness about optimum birth interval , having female index child , death of the index child , breastfeeding of the index child <24 months , use of modern contraceptive , and decision-making by a husband alone when to have a child  were significantly associated with short birth interval at a The overall prevalence of short birth interval among the study participants was high, as more than half of the women had practiced short birth interval, indicating that the majority of the mother and children in the study area are still at high risk of mortality and morbidity associated with short birth interval. Thus, the current findings suggest that interventions that involve the provision of contraceptives and information on its benefit at points need to be adopted to reach the national and global target of maternal and child mortality reduction attributed to short birth interval. Inter-birth interval is defined as the time elapsed between two consecutive births . It has Empirical evidence from various studies identified that a relationship prevails between birth interval and maternal, infant, and child health –11. shorEthiopia has made substantial changes in reducing maternal and neonatal mortality over the last two decades . As a stSome previous studies done in Ethiopia have documented the factors shown to have been associated with short birth interval –29. HoweA community-based cross-sectional study was conducted in the Mieso agro-pastoralist district, Oromia region, Eastern Ethiopia, from 1 to 30 March 2020. The district is located in Eastern Ethiopia, 300 km far from Addis Ababa, the capital city of Ethiopia. The total population  of the district was 139,186. The district is categorized as a semi-pastoral district. Women of reproductive age comprise about 22% of the total population of the district 2 P (1–P)/d2]; by taking a 24.6% proportion of short birth interval among women from a previous similar study conducted in rural Bangladesh  before the actual data collection commencement. Accordingly, a total of 3,258 households with eligible participants were identified. The probability to proportional sampling was used to allocate the total sample size proportional to the size of study subjects in each kebele. Finally, a household with eligible study participants was selected using a systematic sampling technique. Household sampling interval (K) was calculated by dividing the total number of households with eligible participants by the total number of study participants; K = N/n, 3,528/490 = 7.2. Thus, the sampling interval (K) became 7, and the first household with an eligible participant was selected using the lottery method .Data were collected using a face-to-face interviewer-administered structured questionnaire. The interview consisted of the sociodemographic profile of the mother, reproductive history, and awareness about birth interval, breastfeeding, and modern contraceptive-related factors. The questionnaire was designed by reviewing related literature , 26, 32 Data quality assurance mechanisms were carefully developed and implemented at various stages of the study. Initially, the questionnaire was prepared in English and then translated into the local language (Afan Oromo). It was pretested on 5% of the sample size in Asebot Kebele (the nearest non-studied kebele) and checked for consistency as well as appropriateness for the study participants 2 weeks before actual data collection commencement. After the pretest, some modifications were made to the initially prepared questionnaire. The training was given to data collectors and supervisors on the study procedures, data collection steps, and supervision activities for 2 days. Double data entry was done by two data clerks and cross-checked to ensure consistency. Collected data were checked for completeness daily by supervisors.In this study, the birth interval was determined by asking the women to present the birth certificates of the index (previous) and the last (recent) child. Alternatively, if a birth certificate was not available, immunization cards were used. In case both birth certificates and immunization cards were not available, the mother's memory was used to estimate the birth date of the index and the last birth. Next, the birth interval was determined by subtracting the time gap between the two birth dates and expressed in months. To be consistent with the World Health Organization's recommendation  and prevThe period between two successive live births, from birth date to birth date.In this study, a short birth interval was operationalized as an “inter-birth interval of <33 months between two consecutive live births.”A birth interval of 33 months and above between the birth of the index child and the immediately preceding live birth.A child who preceded the last child.p-value of 0.25 or less in bivariate analysis were entered into the multivariable model. Finally, statistical significance was considered at a p-value < 0.05 using an adjusted odds ratio (AOR) with a 95% CI.Collected data were coded, entered, and cleaned using EpiData version 3.1  and analyzed using Statistical Package for Social Sciences, SPSS version 23 . Data cleaning was performed to identify outliers or inconsistencies, errors, and missing values. Both descriptive and analytical statistics were executed. Descriptive statistics such as mean (standard deviation) and median for continuous data as well as frequency and percentage for categorical data were used to describe the participant's characteristics. Both binary and multivariable logistic regression models were used to determine the association between the independent and the outcome variables. The model fitness was checked using the Hosmer-Lemeshow test (P = 0.632). Multicollinearity was also checked using variance inflation factor (VIF) and tolerance to see the correlation between independent variables. First, bivariate analysis was done to determine the association between each independent and the outcome variables as well as variables that were candidates for multivariable analysis. The results of the bivariate analysis were expressed as crude odds ratios (COR) with 95% confidence intervals (CI). All factors that had an association with the outcome variable at a A total of 484 mothers participated in the study, yielding a response rate of 98.8%. The mean age of women at the time of the interview was 31.2 (SD = ± 6.7), ranging from 20 to 49 years. The median age at first marriage for the study participants was 18 years, with the minimum and maximum age of marriage being 12 and 33 years, respectively. The majority of the participants, 449 (92.8%), were Muslims, and 445 (91.9%) were from Oromo ethnic groups. There were 267 (55.2%) women who were housewives. A majority, 442 (91.3%), of the study participants were living with their husbands. Of the participants, 282 (58.3%) had formal education, whereas 188 (38.8%) of their husbands had no formal education. One-third of the study participants, 164 (33.9%), had earned an average monthly income > 5,000 Ethiopian Birr .The median duration of the birth interval between the index and the last child was 31 months. More than two-thirds, 336 (69.4%), of the study participants heard about the optimum birth interval between two successive births. For both mother and child, 357 (76.4%) participants responded that an optimum birth interval has health benefits. Nearly one-third, 166 (34.1) of the participants had 3 or 4 live births. More than half of the participants, 254 (52.5%), delivered their index child at home, and 80 (16.5%) women reported the death of the index child before the conception of the last child. The majority, 465 (96.1%), delivered the index child through the vagina. Moreover, 289 (59.97%) women showed the intention to have more children .The majority, 444 (91.7%), of the women in the study area have breastfed their index child. Among those who had breastfed their index child, 245 (55.2%) participants had breastfed for <24 months. Regarding the study participant's awareness of modern contraceptives, 447 (92.4%) participants had heard about modern contraceptives. nevertheless, only 40.1% of them have reported utilization of modern contraceptives before the conception of their last child. A majority, 178 (91.8%), of the study participants had utilized modern contraceptives for spacing, whereas 16 (8.2%) had used them for limiting births. In addition, 183 (37.8%) of the participants utilized one of the modern contraceptive methods at the time of the interview. The remaining study participants did not utilize modern contraceptives at the time of the interview for different reasons they have mentioned .Of the study participants, 271 (56%) (95% CI: 51.4–60.5) had practiced short birth interval. The median duration of the birth interval was 31 months.p-value of <0.25 in bivariate logistic regression were fitted into multivariate logistic regression. Accordingly, being married under 18 years , having formal education , having had a husband with formal education , having awareness about optimum birth interval , having female index child , death of the index child , breastfeeding of the index child <24 months , use of modern contraceptive before conception of the last child , and decision-making by the husband alone when to have a child  were significantly associated with a short birth interval at a P-value <0.05  of women in the study area were practicing short birth interval, which is consistent with the study conducted in Uganda (52.4%) 6% of wom, Kasala,This study found an association between age at first marriage and short birth interval practice. Women who had married at an age <18 years were more likely to practice short birth interval compared to those who had married at age 18 years or above. This finding is in line with the study done in Jordan  and SoutIn this study, maternal education was significantly associated with short birth interval, indicating that the odds of having short birth interval were lower among mothers who had attended formal education as compared to their counterparts who had no formal education. This finding is consistent with evidence from the studies conducted in Pakistan , Jordan Consistent with the findings of a study done in Arba Minch district, Ethiopia , and DabIt has also been found that the sex of the index child was significantly associated with short birth interval in this study, in which mothers who had a female index child were more likely to have short birth interval compared to mothers who had a male index child. This finding is supported by the studies done in Babol, Iran , NigeriaThe survival status of the index child was another factor associated with short birth interval in this study. Mothers whose index child was dead before conception of the last child were less likely to have short birth interval compared to those with a surviving index child. This finding is in contrast with the findings of the studies done in Uganda , PakistaReproductive decision-making when giving birth was also associated with short birth interval in this study. Women whose husbands decided alone when to have a child were more likely to practice short birth interval than their counterparts. This finding is consistent with a study done in Uganda , which rDuration of breastfeeding was a significant factor associated with a short birth interval in this study. Those mothers who breastfed their index child for <24 months were more likely to have short birth interval compared to their counterparts. This concurs with the findings from studies done in Tigray, Ethiopia , and BorAs found in this study, the odds of having short birth interval were higher among the mothers who had not used modern contraceptives before conception of the last child compared to those who had used it. This finding is supported by the studies conducted in Egypt , Ahvaz, In conclusion, this study illustrated that the prevalence of short birth interval among the study participants was high, as more than half of the women had practiced short birth interval, indicating the majority of the mothers and children in the study area are still at high risk of mortality and morbidity associated with short birth interval. Thus, the current findings suggest that interventions that involve the provision of contraceptives and information on its benefit at points need to be adopted to reach the national and global target of maternal and child mortality reduction attributed to short birth interval. More importantly, ensuring gender equality needs to be a concern, as this would warrant the use of contraceptives and enhance reproductive health decision-making capacity among women. Furthermore, future qualitative studies are required to explore the social and cultural influences on the birth interval that are not addressed in this study.This study has admitted a few limitations. First, this study might be exposed to recall bias since birth interval estimation was mainly based on the mother's memory. Second, being a cross-sectional study design, it does not establish cause-effect relationships between the study variables. Third, the study did not incorporate qualitative exploration of social and cultural influences on birth interval. Moreover, this study recruited a limited sample size, and hence the findings of this study may not be generalizable to women in other areas of Ethiopia.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The study was approved by the Institutional Health Research Ethics Review Committee, College of Health and Medical Sciences, Haramaya University, Ethiopia with approval number (Ref. No: IHRERC/179/2020). Written and verbal informed consent was obtained from all the study participants before the interview.MW, JK, NA, and MD made a significant contribution to the conception of the idea and design, participated in proposal development and data collection, and analyzed and interpreted the data. JK wrote the original draft of the manuscript. JK, NA, and MD reviewed and edited the manuscript for important intellectual content. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Preterm birth remains an ongoing global health issue with over 15 million infants born preterm annually [The purpose of this Special Issue entitled “Health Care in Premature Infants” is to summarize new information from experts in the field of neonatal care along many fronts. Preterm infants, in particular those born before 28 completed gestation weeks, experience a myriad of complications related to their preterm birth which include severe chronic lung disease, significant and resistant patent ductus arteriosus, major intracranial pathology such as intraventricular hemorrhage and ischemia, infections and even challenges from the beginning in resuscitation following a preterm birth.Over the last decade, new efforts have been done to explore optimal approaches in the management of the extreme preterm infant in the delivery setting. Schwaberger et al.  explore Cranial hemorrhages in the small preterm infant continue to pose as major consequences and many strategies are explored in attempts to reduce their incidences. Strategies on protecting the brain are explored by Gross et al.  and PersOf significant importance is who this infant will become and how to support the surviving infant to become a child who is able to function in today’s challenging times and societies around the globe. These are highlighted in different articles in this Special Issue ,7,8,9.The care of the small and very vulnerable preterm infant continues to be challenging and requires consistent review and study ,12,13,14I believe that this issue helps to contribute to consolidating the current body of information with the hopes of enhancing and stimulating further studies on all spectra of care for these vulnerable infants.


Dyslipidemia is a well-recognized risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Growing evidences have shown that compared with the traditional lipid parameters, some lipid ratios may provide additional information of lipid metabolism. Thus, the present study aimed to investigate which lipid index was most related to DKD.2 or urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months. Fasting blood was collected to determine lipid profiles by an automatic biochemical analyzer, and lipid ratios were calculated based on corresponding lipid parameters. Spearman’s correlation analyses were conducted to assess the correlations between lipid indices and kidney injury indices, and binary logistic regression analyses were conducted to explore the relationship between lipid indices and the risk of DKD.This study was a cross-sectional study that enrolled patients with T2D from January 2021 to October 2021. Each participant was screened for DKD, and the diagnostic criterion for DKD is estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 mr = 0.146, p < 0.05) and inversely correlated to cystatin C and UACR . Multiple logistic regression demonstrated that even after adjusting for other clinical covariates, the LDL-C/Apo B ratios were negatively related to DKD, and the odds ratio  was 0.481 (0.275–0.843). Furthermore, subgroup analyses revealed that compared with patients with normal lipid profiles and a high LDL-C/Apo B ratio, the odds ratio of DKD in patients with normal lipid metabolism and a low LDL-C/Apo B ratio was 2.205 (1.136-4.280) after adjusting for other clinical covariates.A total of 936 patients with T2D were enrolled in the study, 144 (15.38%) of whom had DKD. The LDL-C/Apo B ratios were positively correlated with eGFR (In patients with T2D, the LDL-c/Apo B ratio was most closely associated with DKD among various lipid indices, and a lower LDL-C/Apo B ratio was associated with increased risks of DKD among patients with T2D. As one of the major microvascular complications of type 2 diabetes (T2D), diabetic kidney disease (DKD) affects about 20% of patients with T2D . The preIn recent years, growing evidences have shown that compared with the traditional lipid indices, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B) and lipid ratios may provide additional information of lipid metabolism. Apo A1 and Apo B are structural components of HDL-C and atherosclerotic lipoprotein respectively , thus thIn this observational cross-sectional study, patients diagnosed with T2D according to the statement of the American Diabetes Association and screened for DKD were enrolled from the inpatient department of the Second Affiliated Hospital of Nantong University from January 2021 to October 2021 . The folAt enrollment, all subjects completed a questionnaire with the assistance of experienced physicians to collect the demographic data, lifestyle, medication history and diagnosis history of diseases. Body mass index (BMI) was calculated as the weight/height squared. Blood pressure was measured by a standard mercury sphygmomanometer, and the average of three recordings was recorded.2 or a UACR ≥ 30 mg/g lasted for more than 3 months, a DKD diagnosis can be made , and lipid ratios were calculated based on corresponding lipid parameters. Urinary albumin level was evaluated by the immunoturbidimetry method . The algorithm of urinary albumin creatinine ratio (UACR) was the ratio of urinary albumin to urinary creatinine. Estimated glomerular filtration rate (eGFR) was calculated based on the CKD-EPI creatinine-cystatin C equation (2012) . If a pa be made .To explore the relationship between low LDL-C/Apo B ratio and the risk of DKD in T2D patients with normal lipid profiles, the total population was divided into A, B, C and D four groups according to lipid profiles and LDL-C/Apo B ratio. In our laboratory, the reference ranges of lipid metabolism parameters TG, TC, HDL-C and LDL-C were respectively 0.2 - 2.0 mmol/L, 2.9 – 6.0 mmol/L, 1.1 – 1.7 mmol/L and 1.55 – 3.35 mmol/L. Therefore, dyslipidemia was defined as any lipid parameter above the normal ranges described above. Then, a low or a high LDL-C/Apo B ratio was defined according to the median of LDL-C/Apo B ratio (2.8804). Ultimately, group A, B, C and D respectively represented normal lipid profile with a high LDL-C/Apo B ratio, normal lipid profile with a low LDL-C/Apo B ratio, abnormal lipid profile with a high LDL-C/Apo B ratio and abnormal lipid profile with a low LDL-C/Apo B ratio.p < 0.05 was defined as statistical significance.The clinical characteristics of the participants grouped by DKD status were described by mean ± SD, median (25 and 75% interquartile) and frequencies (percentages) for the normally and skewed distributed continuous variables and the categorical variables, respectively. We adopted Student’s t-test to compare differences in normally distributed data, the Mann–Whitney test to compare differences in skewed distributed data and the chi-square test to compare categorical data. Spearman’s bivariate correlation analyses were conducted to analyze the correlations of multiple lipid indices with DKD indicators. As the LDL-C/Apo B ratio was the only parameter related to DKD, multivariate logistic regression analyses were performed to investigate the impact of the LDL-C/Apo B ratio on DKD. Furthermore, the differences in the proportion and odds ratio (OR) were compared among group A, B, C and D by the chi-square test and multivariate logistic regression analyses. All analyses were performed using SPSS statistical software 18.0 . A value of p < 0.05) than T2D patients without DKD. There were no differences in proportion of males, BMI, diastolic blood pressures, uses of other antidiabetic treatments other than insulin, HbA1c levels and lipid indices other than LDL-C/Apo B ratio between patients with and without DKD (p > 0.05).Among the recruited 936 T2D patients, patients combined with DKD accounted for 15.38%. As shown in r = 0.146, p < 0.05), and negatively correlated with cystatin C levels and UACR . Cystatin C levels were significantly correlated with HDL-C levels, Apo B levels, HDL-C/Apo A1 ratios and Apo B/Apo A1 ratios . UACR were positively correlated with TG levels and TG/HDL-C ratios . However, there were no significant correlations between kidney damage indices and total cholesterol (TC) levels and Apo A1 levels .As the LDL-C/Apo B ratio was the only parameter correlated with all kidney damage indices, we thereby constructed multivariate logistic regression analyses to analyze the association between the LDL-C/Apo B ratio and DKD in patients with T2D. As illustrated in p for trend < 0.05). In There were significant differences in the proportion of patients with DKD among Group A, B, C and D  . LDL-C iCompared with other LDL-Cs, less sd-LDL-Cs binding to LDL-C receptors result in sd-LDL-C staying in the circulation longer , and sd-This study had several limitations. First, as this study was a cross-sectional study, the causal relationship between the LDL-C/Apo B ratio and DKD could not be fully elucidated. Second, the LDL-C/Apo B ratio was a proxy for evaluating sd-LDL-C rather than the gold standard, but the large sample size of this study compensated for this deficiency. Third, the generalizability of this study was limited by that this study was based on a Chinese population. Therefore, longitudinal and intervention studies are needed to address the above limitations.In summary, the LDL-C/Apo B ratio was closely associated with the risk of DKD, and a lower LDL-C/Apo B ratio might be a potent risk factor and therapeutic target for prevention and treatment of DKD in patients with T2D. Even in type 2 diabetic patients with normal lipid profile, the LDL-C/Apo B ratio should be routinely assessed.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by The medical research ethics committee of Second Affiliated Hospital of Nantong University. The patients/participants provided their written informed consent to participate in this study.C-FL and Z-HC participated in the design of the study, data collection, analysis of the data, and drafting of the manuscript. X-QW and H-YH conceived of the study, participated in its design and revised the manuscript. W-SL and L-YH participated in data collection. All authors read and approved the final manuscript.The study was supported by the Medical Research Project of Health Commission of Nantong  and the Science and Technology Support Program of Nantong .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Birth asphyxia leads to profound systemic and neurological sequela to decrease blood flow or oxygen to the fetus followed by lethal progressive or irreversible life-long pathologies. In low resource setting countries, birth asphyxia remains a critical condition. This study aimed to develop and validate prognostic risk scores to forecast birth asphyxia using maternal and neonatal characteristics in south Gondar zone hospitals.Prospective cohorts of 404 pregnant women were included in the model in south Gondar Zone Hospitals, Northwest Ethiopia. To recognize potential prognostic determinants for birth asphyxia, multivariable logistic regression was applied. The model discrimination probability was checked using the receiver operating characteristic curve (AUROC) and the model calibration plot was assessed using the ‘givitiR’ R-package. To check the clinical importance of the model, a cost-benefit analysis was done through a decision curve and the model was internally validated using bootstrapping. Lastly, a risk score prediction measurement was established for simple application.Of 404, 108 (26.73%) (95% CI: 22.6–31.3) newborns were exposed to birth asphyxia during the follow-up time. Premature rupture of membrane, meconium aspiration syndrome, malpresentation, prolonged labor, Preterm, and tight nuchal was the significant prognostic predictors of birth asphyxia. The AUROC curve for birth asphyxia was 88.6% (95% CI: 84.6-92.2%), which indicated that the tool identified the newborns at risk for birth asphyxia very well. The AUROC of the simplified risk score algorithm, was 87.9  and the risk score value of 2 was selected as the optimal cut-off value, with a sensitivity of 78.87%, a specificity of 83.26%, a positive predictive value of 63.23%, and a negative predictive value of 91.52%.We established birth asphyxia prediction tools by applying non-sophisticated maternal and neonatal characteristics for resource scares countries. The driven score has very good discriminative ability and prediction performance. This risk score tool would allow reducing neonatal morbidity and mortality related to birth asphyxia. Consequently, it will improve the overall neonatal health / under-five child health in low-income countries. According to the world health organization (WHO) birth asphyxia, neonatal asphyxia, or perinatal asphyxia is defined as the “inability of the newborn to initiate and sustain spontaneous breathing at birth” , 2. BirtGlobally, birth asphyxia/perinatal asphyxia is a foremost long-term consequence in adulthood characterized by an increased risk of cardiovascular diseases , causingOxygen deficit at delivery is the leading cause of brain damage which can lead to severe insults often causing neurodegenerative disease, mental retardation, and epilepsy , 10. TheRisk factors before delivery include severe maternal hypotension or hypertensive disorders while pregnancy , AnteparCurrently, the 2030 sustainable development goals agenda 2030, combines multisystem strategies at the international and national level and has three essential focuses to realize healthy lives and encourage welfare for all ages. Of those goals, one leading aim is to decrease the death rate of neonates to less than 12 per 1000 live births , 24. NevFor better clinical care and public health intervention, understanding the risk probability of birth asphyxia is too essential. In the clinical setting, prediction can be used for the adjustment of lifestyle or therapeutic decisions based on the risk of developing a specific consequence . A conveTherefore, the prediction model is inherently multivariable. Prediction models  are tools that combine multiple predictors by assigning relative weights to each predictor to obtain a risk or probability condition to happen . MultivaThis study was carried out among pregnant women those followed antenatal care in four Hospitals in the South Gondar zone  . Based oThe zone has 8 Hospitals, 96 health centers, 394 health posts, and 118 private health institutions. All of the hospitals give similar services except Debre Tabor general hospital which serves as a referral center for -private and governmental institutions .An institution-based prospective follow-up study was conducted among pregnant mothers from June 1st, 2020 to June 30th, 2021.in this study, all selected pregnant women who followed antenatal care in four hospitals  from June 1st, 2020 to June 30th, 2021 were included.women couldn’t answer the intended questions because of illness and mental problems were excluded.Since there are no previous prediction studies to estimate the sample size, considering the rule of thumb of 10 events per prognostic determinants, , all preData were collected prospectively using pre-tested structured questionnaires. Questionnaires were developed after reviewing relevant literature to include all the possible variables that address the objective of this study. Firstly, the questionnaire was developed in English and translated into the local language (Amharic), and finally, retranslated into English by a language expert. For each Hospital four clinical midwifery health professionals participated as data collectors.Birth asphyxia was defined as an Apgar score of < 7 at the 5th minute with five signs  each of them has 0 to 2 scores , 29, 30.Defined according to r American College of Obstetricians and Gynecologists guidelines as: for nulliparous women > 3 hours with epidural or > 2 hours without; multiparous women > 2 hours with epidural or > 1 hour without. The length of the second stage of labor was determined by subtracting the date and time of delivery from the date and time of 10 cm cervical dilation , 30.Nuchal cord was defined as a loop of the umbilical cord that becomes wrapped around the fetal neck 360 degrees. During delivery, each birth was documented as having a tight nuchal cord, or no tight nuchal cord. ‘tight nuchal cord’ was defined as the inability to manually reduce the loop over the fetal head .was identified when fetal Chorio-amnionic membranes rupture at any time before the beginning of factual labor , 30.this happens after the fetus inhales profuse, particulate meconium. This is foremost secondary to fetal hypoxia which causes amplified peristalsis, relaxation of anal sphincters with the release of meconium into the amniotic fluid; and reflex grasping which leads to aspiration of the meconium into the respiratory system , 30.Birth asphyxia (yes/no).current maternal age maternal education, gravidity, the premature rupture of membrane, meconium aspiration syndrome, malpresentation, prolonged labor, preeclampsia, tight nuchal cord, preterm, have chronic hypertension, hemoglobin level, sex of the child, and birth weight prognostic maternal and neonatal determinants were considered.p-value < 0.10 for the likelihood ratio test to fit the reduced model of easily obtainable determinants. The results were reported as an adjusted odds ratio with 95% CI at a two-sided P-value of less than 0.05.Before data was entered to EPI INFO windows –version 7 statistical software, all the entire interviewed questionnaires were checked manually for completeness and consistency. After that, the data were entered, coded, and cleaned. Finally, the entered data were transferred to R-software for further analysis. Descriptive statistics such as frequency and percentage were performed. Bivariate and multivariable logistic regression was performed to identify potential prognostic determinants. Simple logistic regression was conducted on the derivation data set to investigate the relationship between each predictor and birth asphyxia. We apply the stepwise backward elimination technique with a Model calibration was estimated by plotting the predicted probability against the observed birth asphyxia. Consequently, the model calibration was checked using the ‘givitiR’ R-package. The area under the receiver operating characteristics curve (AUROC) was conducted using the ‘pROC’ R-package to check the model discrimination probability. The AUROC value of 0.5, 0.7, and 1 indicates no discriminative probability, good discriminative probability, and perfect discrimination probability respectively. The internal validation was checked using bootstrapping technique with 2000 iterations of re-samplings. After bootstrapping model’s predictive performance is considered to apply to future similar populations. Through the decision curve, the cost-benefit analysis of the prediction tool was checked.β coefficient) is divided by the lowest β value of the individual variable and rounded to the nearest integer.To develop a straightforward, implementable, and interpretable risk score for birth asphyxia, each estimate  of each category on the risk. Later, the score was transformed into a prediction test classified as high risk or low risk of birth asphyxia. The risk score instrument specificity, sensitivity, and positive and negative predictive value were determined at different values of the risk score cut-points. Finally, using each prognostic determinant risk score value, the probability of birth asphyxia was determined.Overall, a total of 404 pregnant women before delivery and 404 neonates after delivery were followed prospectively for this study. Around two-thirds, 258(63.86%) of the women were found in the age category of 20-29 years, and around one-third of 125 (30.94%) of their educational status were able to read and write. One hundred twenty-one (29.95%) pregnant women were exposed to prolonged labor during labor. One hundred fifteen (28.47%) newborn babies were exposed to meconium aspiration syndrome and fifty-five (13.6%) newborn babies were delivered with low birth weight  . Based on the risk category, 258 newborn babies had a risk score of less than 2; of them, 21 (8.1%) were exposed to birth asphyxia. However, 146 had a risk score of ≥2, the 87 (59.6%) experienced birth asphyxia. The sensitivity and the specificities were 78.87 and 83.26% respectively with a positive predictive value of 63.23% and negative predictors of 91.52% (Table Probability of birth asphyxia = (2*Premature rapture of membrane) + (1* Meconium aspiration) +  + (1* Prolonged labor) + (1*preterm) + .The present study reviled that the incidence of birth asphyxia was 26.7%. In this study, the most prominent aim was to develop and validate a simplified clinical prognostic risk score system for birth asphyxia using 7 maternal and neonatal characteristics during pregnancy without the need for any sophisticated laboratory or imaging test. The combination of six maternal and neonatal characteristics produces a true prediction accuracy of 0.86, which is a sweeping tool to predict birth asphyxia according to diagnostic accuracy classification .To achieve the highest aspiration model, premature rupture of membrane, meconium aspiration syndrome, malpresentation, prolonged labor, tight nuchal cord, and preterm was the prognostic determinant of birth asphyxia. A clinical assessment and laboratory examinations are required to evaluate and manage the asphyxiated newborn before the problem advanced to irreversible organ damage and death. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics allocate a neonate to be asphyxiated if the succeeding circumstances are satisfied: Umbilical cord arterial pH < 7; Apgar score of 0-3 for longer than 5 min; neurological manifestations ; and multisystem organ dysfunction, e.g., cardiovascular, gastrointestinal, hematological, pulmonary or renal system. At the same time, the overhead standards could be valuable and valid in developed countries, however, they cannot be practically made use of in resource-limited countries .Therefore, this study offers an enduring solution (appropriate risk score measurement) using the Youden index cut-off point, which has a supreme true positive rate (sensitivity) and true negative rate (specificity).This prediction model has an outstanding negative predictive value and true negative rate (specificity), signifying that an advantageous preliminary screening tool to recognize the jeopardy of the neonate for birth asphyxia. This is the primary study that develops and validates an early warning risk score tool for the prediction of birth asphyxia in low-income countries. For this current prediction study, the premature rupture of the membrane has been a high predictive value for birth asphyxia. Simultaneously this finding was supported by several studies which were conducted in Colombia , Al-DiwaThe agreement could be accepted the fact that whiles the fetal membrane ruptured impulsively, extemporaneous amniotic liquid occurs lengthways with umbilical cord prolapse and compression. The longer the distance of the rapture of membranes, the more likely the uterus increases the incidence of fetal and maternal morbidity suffering, and mortality . MeconiuThe conceivable explanation, the occurrence of meconium in the amniotic fluid may cause aspiration of meconium-stained amniotic fluid to happen, and this can block minor airways, deactivate surfactants, chemical inflammation, and apoptosis of the pulmonary tissues, and may also constrain surfactant production, causing in a pulmonary air leak and birth asphyxia . Like otBabies being born earlier than 37 completed weeks of gestation may be exposed to birth asphyxia due to an unsatisfactory amount of surfactant in the lungs . SurfactLastly, malpresentation was one of the prognostic determinants of birth asphyxia. Consequently, this study was supported by , 41. TheThis study shows the possibility of predicting birth asphyxia using a simple prediction model constructed from easily accessible and applicable maternal and neonatal characteristics, including premature rupture of the membrane, meconium aspiration, malpresentation, prolonged labor, preterm and tight nuchal cord). The derived score has good sensitivity for predicting birth asphyxia. It has n very good discriminative ability (accuracy). This new and relatively simple birth asphyxia risk score had a good prediction performance in Ethiopia. This is an important tool for predicting birth asphyxia.Therefore, this score may prove to be a better model for application in low and middle-income countries. However, before introducing it to clinical and public health practices, further external validation  studies are needed to improve the prediction accuracy and applicability of the risk prediction tool. Our prediction model constitutes variables that are easily applicable and have reasonable accuracy to be used by both mid-and lower-level health professionals in each type of health institution. Findings from this study should be interpreted from the perspective of the following limitations. Frist limitation, as a single site (one zone) study, it is confined to a single area, which needs external validation before using it in another context. Second, pre-pregnancy body mass index, gestational weight gain, and maternal nutritional status were not assessed.


This retrospective study was performed over 6 months, including newborns with a gestational age between 34–36 weeks and 6 days in the Department of Obstetrics, Gynecology and Neonatology, Alessandrescu-Rusescu National Institute of Mother and Child Health. The following variables were assessed: infants' gestational age, delivery mode, respiratory morbidity, and the need for respiratory support. During the mentioned period, 112 late preterm infants were born, out of whom 9.8% represented late preterm infants conceived by in vitro fertilization. The delivery mode of late preterm infants conceived by in vitro fertilization was exclusively by C-section (100%) compared to those conceived spontaneously (44.5%). 18.1% of IVF late preterm infants developed transient tachypnea of the newborn. In the non-IVF group, respiratory distress syndrome was present in 5.9% and transient tachypnea in 33.6% of cases. No IVF late preterm infant required hospitalization in neonatal intensive care for more than 3 days, compared to 19.8% of naturally conceived late preterm infants. Respiratory distress syndrome very seldom occurs in late preterm IVF infants due to prenatal prophylactic treatment with corticosteroids. Respiratory pathology is rarely present due to very careful monitoring during pregnancy, the presence of a neonatal team in the delivery room for possible resuscitation, and providing proper care according to the good state of health during the short, one-week hospitalization.This study aimed to identify the incidence of  In vitro fertilization (IVF), a method of assisted reproduction techniques (ART), was perfected by the British Scientist Professor Robert Geoffrey Edwards, allowing on July 25th 1978, in London, the birth of Louise Joy Brown, the first child conceived through this method. IVF is considered one of the greatest medical achievements of the 20th century, “one of the fastest growing areas of medicine, having expanded far beyond the imaginations of those who pioneered the technique that led to the birth of Louise Brown” [e Brown” .Preterm birth is defined as the birth of a child before 37 fulfilled weeks of gestation and is the leading cause of neonatal mortality . New gloThe British Medical Journal defines prematurity categories based on gestational age (GA) (weeks-w): extreme prematurity <28w), severe prematurity (28–31w), great prematurity (32–33w), and late prematurity (34–36w). This classification was necessary because LPT represent 8–9% of the newborns and 74% of the preterm neonates, their incidence rising by 20% since 1990 . Late-prw, severein vitro fertilization of late preterm newborns (IVF-LPT) and the presence of respiratory pathology in this category of preterm newborns compared with those conceived naturally (non-IVF newborns).The objective of this retrospective study was to identify the incidence of The retrospective study was performed in 2019 for 6 months at the Department of Obstetrics, Gynecology and Neonatology, Alessandrescu-Rusescu National Institute of Mother and Child Health, Bucharest, Romania. We included 112 IVF and naturally conceived infants admitted to our department. The following were monitored: infants' gestational age, delivery mode, respiratory morbidity, the need for respiratory support, and mortality. Data were collected from medical records and analyzed using IBM SPSS Statistics v20.0.0, performing descriptive statistics.During the mentioned period, there were 44 IVF infants recorded, 61.4% of whom were born preterm. Late preterm infants (LPT) accounted for 25% of the total number of IVF infants and 40.7% of those who were born preterm .During the study period, 112 preterm infants were born at a gestational age of 34–36 weeks and 6 days (LPT). LPT conceived by IVF accounted for 9.8% of the total number of LPT recorded during the study. According to gestational age, in both groups, LPT infants, in most cases, were born at 36 weeks of gestational age .vs. 93.1% in the non-IVF group; the breech presentation was 45.5% in the IVF-LPT group vs. 6.9% in the non-IVF LPT infants.The incidence of IVF LPT newborns by gender was: female – 81.8%, male – 18.2%. In the non-IVF group, 51.4% were female, and 48% were male newborns. Regarding birth weight (BW), 54.5% of IVF-LPT infants had a BW over 2500 grams and 45.4% between 2000–2500 grams. In the non-IVF-LPT group: 52.4% had BW >2500 grams, 40.5% 2000–2500 grams, 5.2% between 1500–1999 grams and 1.9% were under 1500 grams. A big difference was registered regarding fetal presentation: the percentage of cranial presentation in IVF-LPT infants was 54.5% There were differences in the Apgar score between the two groups: IVF-LPT infants had an Apgar score under 7, compared to the non-IVF group in which 5.9% had an Apgar score between 4–6  and 1.9% had an Apgar score under 3  .Resuscitation at birth was not required in IVF-LPT infants, in contrast to the non-IVF-LPT infants who required resuscitation  at 10.9%.in vitro fertilization, according to the results of studies in other countries, are more likely to require respiratory support, require more aggressive respiratory support and receive surfactant indicative of true respiratory distress syndrome [Respiratory pathology in LPT remains at higher risk when compared with term infants . This insyndrome . In our The low incidence of respiratory pathology and required oxygen therapy in IVF-LPT newborns was probably due to the prophylactic corticoid therapy on 100% of the pregnant IVF patients and very well-supervised IVF pregnancies .versus 5.9% in the non-IVF group , resuscitation at birth, and being prone to RDS.IVF late preterm infants have an increased risk for respiratory morbidity, inversely proportional to gestational age. LPT newborns are at increased risk for respiratory distress syndrome (RDS), transitory tachypnea of the newborn (TTN), apnea, pulmonary hypertension (PPHN) and pneumothorax compared with newborns delivered at term .Even if concerns have been raised over the past years, IVF has been used more frequently in recent years. Further research is needed to effectively evaluate IVF newborns and their risk.In our study, respiratory distress syndrome rarely occurred in late preterm IVF infants due to prenatal prophylactic treatment with corticosteroids. Respiratory pathology is rarely present due to careful monitoring during pregnancy, the presence of the neonatal team in the delivery room for possible resuscitation and providing proper care during the short hospitalization.


Homo sapiens, but is also an important health risk indicator. Addressing a lack of comparative studies on head size and its variability in term and preterm neonates from different populations, we aimed to examine neonatal HC by gestation according to a regional reference and a global standard. Retrospective analysis of data on neonatal HC obtained from the Lithuanian Medical Birth Register from 2001 to 2015 . The varying distribution by gestation and sex was estimated using GAMLSS, and the results were compared with the INTERGROWTH-21st standard. Mean HC increased with gestation in both sexes, while its fractional variability fell. The 3rd percentile matched that for INTERGROWTH-21st at all gestations, while the 50th and 97th percentiles were similar up to 27 weeks, but a full channel width higher than INTERGROWTH-21st at term. INTERGROWTH-21st facilitates the evaluation of neonatal HC in early gestations, while in later gestations, the specific features of neonatal HC of a particular population tend to be more precisely represented by regional references.Neonatal head circumference (HC) not only represents the brain size of  Hence, HC at birth is an indirect measure of brain growth in utero that helps, in general, to evaluate foetal growth. Although at birth the human brain is 25% of its adult weight and continues growing until the age of approximately 10 years, HC is usually of interest primarily in infancy when the head growth velocity rate is maximal1.Head circumference (HC) is a routine paediatric measurement that “acts as a proxy for brain size”8. Greater HC at birth and faster postnatal head growth are associated with better neurocognitive and intellectual abilities in adolescence and young adulthood rather than birth weight per se5. In contrast, small HC at birth is related to the increased male risk of low intellectual performance6, emotional and behavioral disorders8, and higher arterial, especially systolic, blood pressure9. Considering neonatal HC an important health risk indicator for various periods of human development, an adequate HC growth assessment can facilitate not only the identification of infants at highest risk for long-term growth impairments, but also the choice of timely preventive health measures10.Moreover, newborn HC, especially in those born preterm, is a significant health indicator. HC at birth and its postnatal growth dynamics are correlated with short-term and long-term health outcomesHomo sapiens. Thus it is likely to be more constant and less variable than other body size traits in a given population. On the other hand, postnatal growth is widely variable, and body size indices differ across geographic regions, populations12, or due to socio-economic circumstances15.Head size with its huge encephalisation ratio is the main characteristic of 16 found that the interpretation of the postnatal growth of very preterm infants differed considerably depending on the four different references that were used: the proportion of microcephaly in very preterm infants varied from 3 to 25%. These distinct interpretations may lead to misdiagnosis and affect treatment and health monitoring strategies in clinical practice.Thus tools for growth monitoring should be age- and sex-specific growth references or growth standards. Growth references describe how children from a particular region are growing, while growth standards present how children should grow under almost optimal conditions. The choice of growth reference for clinical practice is important for the evaluation of individual growth pattern. V. Neubauer et al.17. In 2008, the International Foetal and Newborn Growth Consortium for the 21st Century  launched a multi-country project to develop similar prescriptive standards for foetal growth, neonatal size and postnatal growth of preterm infants19.In 2006, the World Health Organization (WHO) published its child growth standards for children under five years. Subsequently the use of the WHO charts for particular countries or regions has been widely discussed13 have considered the evaluation of postnatal growth in newborns. So far, there is a lack of studies comparing head size and its variability in term and preterm neonates from different populations and geographic regions. There is no clear evidence on whether global standards for newborn HC apply to neonates from all geographical areas. Moreover, the increasing prevalence of caesarean section in clinical practice, with fewer neonates born vaginally, described by M. Odent20 as a phenomenon of a sudden disappearance of the “evolutionary bottleneck”, may lead to increased variability in HC at birth.Many recent studiesIn this context, the aim of the present study was to analyse HC in Lithuanian newborns according to their gestational age and sex and to compare the results with those provided by the IG-21 study and other countries with evolutionary insights on variability.21) were removed from the analysis. In total, the cohort sample size of 423 999 newborns was derived. The sampling procedure and exclusion criteria are presented in a flow diagram .Our study examined the anonymized database from the Health Information Center of the Institute of Hygiene in Vilnius, Lithuania. The study was based on the Lithuanian Medical Data of Births registered from the year 2001 to 2015 and included all data on singleton liveborn newborns between 24 and 42 completed weeks of gestational age (GA), retrieved from medical records with the total duration of pregnancy in weeks. We excluded all cases of multiple births, stillbirth, undetermined gender, incomplete data  or newborns with major congenital malformations and syndromes. The cases with the main newborn anthropometric indices  incompatible with gestational age (more or less than Mean (M) ± 3 Standard Deviations (SD) following the WHO standards22.The statistical analysis of data was performed using the standard statistical programs . The major parameters of descriptive statistics and percentiles of HC by GA and sex for Lithuanian newborns were calculated. The coefficient of variation (CV) was calculated and used in the comparative analysis with the foreign studies23. The LMST method (BCT distribution) were applied to the data obtained on each sex and each measurement, respectively. The resulting main percentiles  were compared with IG-21 from 24 weeks. The analysis was carried out using the GAMLSS package (version 4.3–3) of R 4.0.3 software (www.r-project.org).GAMLSS was used to estimate the distribution applied to smooth the 3rd, 10th, 25th, 50th, 75th, 90th and 97th HC percentiles by GA and sex separately24 were presented for both sexes for every gestational week and day separately , while GA of the present study was recorded as complete gestational weeks . Therefore, the comparative analysis of the present study with the IG-21 project by GA was made by comparing the mean of HC at the specific gestational week of IG-21. The differences between the means were calculated using t-test. A p-value of < 0.05 was considered to indicate a statistically significant difference.The comparison of the present data on HC of Lithuanian neonates with the data provided by the IG-21 project was conducted. Both the published standards of IG-21 projectThe data were also expressed as sex and gestation specific Z-scores using IG-21 as reference.The study was granted the approval of the governmental institution the Lithuanian Bioethics Committee  and was performed in accordance with the relevant ethical guidelines and regulations.The sample size of our study Table  increase19 from 31 weeks for boys and 32 weeks for girls, the difference increasing with gestational age .The mean HC of Lithuanian preterm and term newborns was greater than for IG-21The 3rd, 10th, 25th, 50th, 75th, 90th, and 97th smoothed gestational age- and sex-adjusted percentile curves for HC of Lithuanian newborns are shown in Fig. Comparing the 3rd, 50th and 97th Lithuanian HC percentiles by sex and gestation with those for IG-21 confirmed the pattern seen in Table 10. There is a lot of discussion recently concerning the choice of whether regional or global, age and sex-specific growth references or growth standards should be used for different populations13. Our study revealed that in late preterm and term periods, with a typically smallest neonatal head circumference (HC) variability within a population, the differences between populations are the most pronounced   was examined. According to different studies) Tables  and 2. H30, HC is expected to be more strongly genetically determined and anthropometrically limited by the indices of the bony birth canal. Even though the newborn HC should be less influenced by internal or external factors than birth weight or length, many studies have raised the discussion on the complex interaction between the intrinsic and extrinsic factors in the development of neonatal HC32. Furthermore, females with a large head, who are likely to give birth to neonates with a large head, were found to possess birth canals that are shaped to better accommodate large-headed neonates29. Moreover, it is already known that variation in the shape of the female pelvis is significantly geographically structured33.As the shape of the human pelvis is often interpreted as an evolutionary compromise between bipedal locomotion and childbirth of a highly encephalized neonate29. In the study of R. G. Tague34 femoral length/stature in females showed a significant, positive partial correlation with the anteroposterior diameter and shape of the pelvic inlet. A recent Swedish study35 proved this relationship from the clinical point of view reporting decreasing risk of caesarean section (CS) with increasing maternal height after adjustment for maternal age, BMI, gestational age, parity, high birth weight and country of birth. With average Swedish women’s height of 166.1 cm, maternal height of 178–179 cm was associated with the lowest risk of CS , whereas height below 160 cm explained 7% of CS cases35. It is worth mentioning that according to the NCD Risk Factor Collaboration36, Lithuanian women are among the tallest women in the world with an average height of 167.6 cm. The comparative results of the female average height reflect the differences found between the mean neonatal HC from different populations, as shown in Table 36. This supports the previous study’s findings29 that perhaps maternal height is linked to pelvic size, particularly the size of the birth canal, and through that to the neonatal HC. This possible relationship between neonatal HC (cm) at term (40 weeks of gestation) and average women’s height across compared countries is presented in Fig. 35.What is more, the pelvis shape was found to be significantly associated with the stature for taller women having a more oval pelvic inlet and better accommodating a larger foetal head37 revealed a similar pattern and found the trajectory of the third percentile parallel with the IG-21 study until the term period. The sample size of the IG-2119 reference was only modest for < 37 weeks gestation, and the later study on very preterm neonates ’should be interpreted with caution given the small sample size’24. This may explain a “wave” at 33 gestational weeks observed in the percentile curves of IG-21  had more similarities not only in the third, but also in the 50th and 97th percentiles of HC. The Brazilian study38, the gap would be smaller. In line with other studies39 evaluating the influence of growth curves used for the distribution of HC, our study also claims that the important consequences could have been triggered by the percentile misclassification. Therefore, from the standpoint of clinical practice, to predict the course of HC higher percentiles in moderate or late preterm periods and, especially, in Lithuanian term newborns, regional standards should be used.As for the other extreme, the 97th percentile, above which infants would be diagnosed with macrocephaly, a large gap between the curves of both studies of more than 1 cm from late preterm to post-term was detected which could lead to an overestimation of macrocephaly in our cohort. If we compared our results with the HC curves provided by the Centers for Disease Control and Prevention (CDC)17. Human growth is determined by inherited factors, and the significant variability of foetal growth in utero between ethnic groups supports this statement31. Therefore, the IG-21 project charts based on the idea that foetuses, infants, and children grow similarly all over the world under ideal nutritional, environmental, psychological living conditions have been widely discussed. A number of studies46 recently have compared their foetal and neonatal national growth references with the IG-21 study that was recently published, and obtained diverse results. Some studies did not find appreciable differences with IG-21 for newborn HC40 or a statistically significant difference was observed only of female HC in the 97th percentile32. While others determined that IG-21 standards for foetuses47 were found to be unrepresentative for regional populations leading to considerable overdiagnosis of foetal microcephaly or misclassification of infant birth size46 and a conclusion that regional validation was needed prior to the implementation of IG-21. We found that global standards like INTERGROWTH-21st might facilitate the evaluation of neonatal head circumference in early gestations, while in later gestations, the specific features of neonatal head circumference of a particular population tend to be more precisely represented by regional standards.Accordingly, the question has been raised by scientists whether children’s growth references should be global, or specific to different populations: ’it has become apparent that a single “global” reference fails adequately to mirror the diversity in human growth’Therefore, we suggest taking into consideration the regional standards for neonatal head circumference in order to better evaluate a possible clinical pathology. It is important to stress that over the process of evolution, neonatal body size and head circumference have adapted to the mother's body size, especially her pelvis, as a result of diverse adaptation mechanisms common to different populations in different geographical areas and under different living conditions.The closer to the late preterm—term period, the greater the differences between neonatal head circumferences in different populations. This threshold is slight, but it marks the inevitable influence of the evolutionary mechanisms that operate to first concentrate on vital biological capacities for neurodevelopment and only then allow genetics, ethnicity and other complex factors to influence the variability of neonatal head circumference.Consequently, the global standards as IG-21 may serve for the evaluation of HC in early gestations, taking into account that most countries do not have a possibility to construct their own references due to small numbers of neonates born extremely preterm. In later gestations, regional standards more precisely represent the specific features of the neonatal HC of a particular population.Supplementary Information 1.Supplementary Information 2.


Isolated involvement of brain with hydatid disease is a rare manifestation and occurs in only 1-2% of all Echinococcus granulosus infections. Here we present a young female of 16 years with primary intra cranial hydatid cyst without any extracranial involvement in the liver or lung. The patient was managed surgically and anti-helemthic medications were given, and the patient was discharged. The objective is to report a rare case of primary solitary hydatid cyst of brain. The incidence of isolated hydatidosis of brain is rare and should be considered as a differential diagnosis in endemic areas. Isolated Hydatidosis of brain is managed surgically and has to be removed carefully without spillage with postoperative medication to reduce the risk of recurrence. Echinococcus tapeworm larvae (metacestodes) infecting humans [Echinococcus granulosus is the most prevalent kind of Echinococcus infection, while Echinococcus multilocularis is the less common variety [Echinococcus granulosus infections. Brain hydatidosis disease is more common in children and young adults [Hydatidosis is a zoonotic disease caused by g humans . Echinoc variety . Humans  variety . The liv variety . Isolateg adults . In thisPatient information: a 16-year-old female who is a resident of Vidarbha region of Maharashtra presented to Acharya Vinobha Rural Hospital, Wardha with complaints of 2 episodes of generalized tonic-clonic seizures with a past history of headache on the left side since last 1 year, she did not give any history of pain in abdomen or shortness of breath.Clinical findings and timeline: general physical and systemic examination of the patient was unremarkable.Diagnostics assessment: MRI of brain with contrast showed well-defined peripherally enhancing rounded predominantly cystic lesion of size 5 x 4.9 x 4.8 cm in left fronto-temporal region with multiple daughter cysts within a large cyst suggestive of intra-cerebral hydatid cyst. There was also evidence of peri-lesional edema causing mass effect in the form of effacement of left ventricle and midline shift of 9 mm  and Magnetic resonance imaging (MRI), while histological testing is still the gold standard. The CT pictures demonstrate a hypodense cystic lesion with neither edema or contrast enhancement perilesionally. T1-weighted pictures show a hypointense cyst, whereas T2-weighted images show a hyperintense cyst with a hypointense halo surrounding its capsule . The dauThe aim of surgery for a hydatid cyst is to remove the cyst in toto without rupture, preventing recurrence and anaphylactic reaction. Dowling's approach is currently the most successful and effective method used nowadays. The cyst is delivered using this procedure by lowering the operating table's head and injecting warm saline between the cyst and the surrounding brain parenchyma. To lessen the risk of recurrence after a rupture, surgeons should clean the surgical site with hypertonic saline and apply chemotherapy such as albendazole or mebendazole . AlbendaPrimary brain hydatid cysts are uncommon; however, they must be regarded as a differential diagnosis in endemic regions. Surgery is the treatment of choice and must be removed carefully without spillage with postoperative medication to reduce the risk of recurrence.