To evaluate the impact of small for gestational age (SGA) on outcomes of very preterm infants at Groote Schuur Hospital (GSH), Cape Town, South Africa.Data were obtained from the Vermont Oxford Network (VON) GSH database from 2012 to 2018. The study is a secondary analysis of prospectively collected observational data. Fenton growth charts were used to define SGA as birth weight < 10th centile for gestational age.Mortality , bronchopulmonary dysplasia , and late-onset sepsis  were higher in the SGA than in the non-SGA group.Small for gestational age infants have a higher risk of mortality and morbidity among very preterm infants at GSH. This may be useful for counseling and perinatal management. Small for gestational age (SGA) is defined as a birth weight that is below the 10th percentile for gestational age .Small for gestational age is commonly used as a proxy for intrauterine growth restriction and, in settings with a high prevalence of SGA, it is more likely to be a result of intrauterine growth restriction rather than being constitutionally small . IntrautIn LMICs, mortality risk associated with being premature and SGA is substantially higher than for either alone, with these infants having a 10–40 times higher risk of mortality in the first month of life when compared with term and appropriate for gestational age infants . We sougThe study is a secondary analysis of prospectively collected observational data. GSH is a public hospital with a highly specialized public neonatal unit. There are 75 neonatal beds of which 20 are for intensive care. The neonatal unit admits up to 2,000 babies a year and approximately 500 infants are VLBW. We obtained data from the Vermont Oxford Network (VON) GSH database from 2012 (when we joined the Network) to 2018. VON is a non-profit, voluntary worldwide collaboration dedicated to improving the quality, safety, and value of neonatal intensive care . The datSmall for gestational age was defined as a birth weight below the 10th centile and non-SGA as birth weight ≥the 10th centile using sex-specific Fenton growth charts . Non-SGAInfants were considered to have exposure to antenatal corticosteroids if betamethasone, dexamethasone, or hydrocortisone was administered intramuscularly or intravenously to the mother during pregnancy at any time prior to delivery. Mothers were reported to have received prenatal care if any obstetric care was provided prior to the admission during which the birth occurred. Maternal hypertension was defined as chronic or pregnancy-induced hypertension (above 140 systolic or 90 diastolic), with or without edema or proteinuria. Eclampsia and pre-eclampsia were considered the forms of pregnancy-induced hypertension.2 in the first 48 h of life despite continuous positive airway pressure (CPAP) or invasive mechanical ventilation. Papile’s criterion  was defined as respiratory distress from birth with the need for >35% Fioriterion  was usedriterion . Severe riterion  documentriterion . Necrotiriterion .a priori, were included in each model without stepwise or backward selection.All analyses were conducted in Statistical Analysis System 9.4. Logistic regression with a Poisson distribution and log link was used to produce risk ratios for each outcome adjusted for sex, antenatal steroid exposure, inborn/outborn status, and gestational age in weeks . All adjA total of 1,879 infants with VLBW between the gestational ages of 27 weeks 0 days and 30 weeks 6 days were admitted to GSH NICU between 2012 and 2018. The prevalence of SGA among the study population was 12.7%. The mean gestational age for both infants with SGA and non-SGA was 29 weeks. The mean birth weight in the SGA group was 799 and 1,083 g in the non-SGA group. The majority (99%) of the non-SGA group was AGA with only 20 infants being LGA. The mothers of infants with SGA were more likely to have received antenatal steroids (73.6% vs. 66.4%) and to have hypertension (60.1% vs. 40.4%). During the study period, 372 of the infants demised before being discharge home with an overall mortality rate of 19.7%. The mortality rate was significantly higher in the SGA group at 28.9% vs. 18.5%  when compared to the non-SGA group. BPD, NEC, and LOS were significantly higher in the SGA group. Among the infants with SGA, 217 were categorized into symmetrical  and asymmetrical  SGA (22 infants were missing birth head circumference). There were no statistically significant differences in mortality or morbidities when these two groups were compared.In our study population, 12.7% of the infants were SGA as defined as weight less than the 10th centile at birth by the Fenton growth charts . This isWe found the mortality rate to be significantly higher among infants with SGA as compared to infants with non-SGA. The increased risk of mortality is similar to the mortality that Li-Yi Tsai et al. found in Taiwan, which was a middle-income country at that time . OverallLevels of BPD are very low at GSH  but we fNecrotizing enterocolitis is the most serious gastrointestinal complication affecting infants with VLBW. The risk of NEC was higher in the SGA group when looking at the entire study population but when we analyzed the risk among survivors the difference between the groups did not reach statistical significance. This finding suggests a high mortality for SGA babies who develop NEC. Bhoghossian et al. also found an increased risk of NEC among infants with SGA . RedistrInfants with SGA in our study were more prone to developing late-onset neonatal sepsis. Troger et al. had similar findings and this was elucidated by the increased use of central venous catheters and a longer time to reach enteral feeds in the SGA population . PreviouAs more premature infants survive due to improved neonatal care, the incidence of ROP has been increasing and South Africa has become a part of the third epidemic of ROP . BhoghosA limitation of this study is that only 30–40% of infants in our institution have an early ultrasound scan (<20 weeks’ gestation). When an early ultrasound was not available, Ballard score or postnatal foot length was used to estimate gestational age, which may be less accurate by up to 2 weeks . Other lGroote Schuur Hospital, a public academic hospital in a middle-income country, had a 12.7% rate of infants with SGA VLBW, higher than often reported in high-income countries. Infants with SGA VLBW at GSH had approximately two times the risk of mortality as compared to their AGA counterparts and increased morbidities. These findings are useful for perinatal decision-making and counseling of parents.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was approved by the Human Research Ethics Committee of the Health Sciences Faculty of the University of Cape Town (R117/2020). Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.MM was responsible for designing the study proposal, writing the protocol and report, interpreting results, and looking up references. DE was responsible for designing the study proposal, editing the protocol and report, interpreting results, and updating reference list. EE was responsible for designing the study proposal, analyzing the data, designing tables and figure, and editing the report and references. NR was responsible for designing the study proposal and editing the report. LT was responsible for designing the study proposal, editing the protocol and report, interpreting results, designing


We compared birth injuries for spontaneous vaginal (VD) and caesarean section (CS) deliveries in preterm and term pregnancies.A retrospective cohort study was conducted in a single tertiary center, between January 1st, 2007, and December 31st, 2017. The study included 62330 singleton pregnancies delivered after 24 0/7 weeks gestation. Multivariable analyses compared trauma at birth, birth hypoxia and birth asphyxia in term and preterm deliveries, stratified by mode of birth, VD versus CS. Main outcome measure was trauma at birth including intracranial laceration and haemorrhage, injuries to scalp, injuries to central and peripheral nervous system, fractures to skeleton, facial and eye injury.The incidence of preterm deliveries was 10.9%. Delivery of preterm babies by CS increased from 37.0% in 2007 to 60.0% in 2017. The overall incidence of all birth trauma was 16.2%. When stratified by mode of delivery, birth trauma was recorded in 23.4% of spontaneous vaginal deliveries and 7.5% of CS deliveries . When considered all types of birth trauma, incidence of trauma at birth was higher after 28 weeks gestation in VD compared to CS . There was no difference in the incidence of birth trauma before 28 weeks gestation between VD and CS . Regarding overall life-threatening birth trauma or injuries at birth with severe consequences such as cerebral and intraventricular haemorrhage, cranial and brachial nerve injury, fractures of long bones and clavicle, eye and facial injury, there was no difference in vaginal preterm deliveries compared to CS deliveries .CS is not protective of injury at birth. When all types of birth trauma are considered, these are more common in spontaneous VD, thus favoring CS as preferred method of delivery to avoid trauma at birth. However, when stratified by severity of birth trauma, preterm babies delivered vaginally are not at higher risk of major birth trauma than those delivered by CS. Birth trauma is defined as all mechanical or hypoxic neonatal injuries sustained during labour and delivery. The rate of birth trauma was estimated anywhere between 2.45 and 41.16 per 1000 births. The functional sequelae remain responsible for a significant neonatal morbidity and mortality [Infant mortality result of birth trauma has declined over the past decades in comparison with historical references, reflecting in part the technological advancements in obstetrics that allow early recognition of risk factors using ultrasonography and fetal monitoring . Most ofInternational Classification of Diseases, Tenth Revision (ICD-10) from the birth trauma section, codes that represent outcomes considered avoidable through practice modification. It is our hope that the findings current study will contribute to advance the knowledge in the field, facilitating changes in medical practice and offering support in the decision-making process for obstetricians regarding the mode of delivery for preterm babies.This study was designed to assess the contemporaneous frequency of birth trauma and its consequences in singleton preterm births, in cephalic presentation. We hypothesized that delivery of preterm fetuses by CS would be associated with a lower incidence of neonatal birth trauma. Thus, we examined the rates of birth trauma, using all codes of We performed a 10-year retrospective cohort study of all singleton spontaneous cephalic deliveries from a single tertiary center in Romania, between January 1st, 2007 and December 31st, 2017 on. Our university maternity hospital serves as referral center for all maternity hospitals in northeast Romania. We used as data source the electronic medical records of hospital admissions for delivery from 67,348 mother and baby dyads.Information of maternal sociodemographic characteristics, obstetrical events at delivery, and neonatal outcomes was abstracted from the electronic medical records. The information retrieved was based on hospital discharge diagnosis codes, classified using the International Statistical Classification of Diseases and Related Health Problems, version 2010 (ICD-10). Additional details about the ICD-10 codes are provided in the Appendix  Tables. Detailed data related to demographics , pregnancy , and newborn  were abstracted from the electronic database.Our study population included women with singleton, cephalic presentation, who delivered preterm, between 24 + 0/7 weeks to 36 + 6/7 weeks gestation, and at term, ≥ 37+0/7 weeks gestation. Women were excluded from this study if they had multiple pregnancies, presentation other than cephalic, newborns who were not delivered in our center, newborns with pre-existing condition or congenital malformations. Women with missing information were excluded from the study. Infants delivered by vacuum or forceps were excluded from this analysis due to the known possibility that the operative deliveries could independently increase morbidity and mortality for those neonates. Only women who had a CS or spontaneous VD were included in the study.The final study population was represented by 62.330 mother-newborn dyads.Using World Health Organization classification of preterm birth, the participants were classified in four groups based on the gestational age at birth: extremely preterm, 24 + 0/7 to 27+ 6/7 weeks; very preterm, 28 + 0/7 to 31+ 6/7 weeks; moderate to late preterm 32 + 0/7–36 + 6/7 weeks, and term pregnancies, 37 + 0/7–42 + 0/7 weeks. Routine first trimester dating US was used to calculate estimated date of delivery and gestational age at delivery.Maternal sociodemographic characteristics were categorized as follows: maternal age was divided in five categories ; ethnicity in two categories , parity in two categories , location in two categories . Maternal comorbidities included in the full model as confounding variables included pre-existing diabetes mellitus, gestational diabetes mellitus, chronic hypertension, pregnancy-induced hypertensive disorders, preterm labour, preterm rupture of membranes, chorioamnionitis, and urinary tract infection. We combined diabetes and gestational diabetes for the simplicity of the analysis. Pregnancy-induced hypertensive disorders included pregnancy induced hypertension, preeclampsia, and HELLP syndrome. There was a small number of women with pre-existing hypertension, and this group was amalgamated with pregnancy-induced hypertensive disorders for meaningful comparisons.The mode of birth was classified in two categories: CS and VD, with CS delivery used as the reference category.The year of delivery was included in the descriptive analyses to illustrate how the incidence of CS delivery changed over time in our cohort.Cerebral hemorrhage due to birth trauma, included subdural, cerebral, subarachnoid, tentorial hemorrhage, lacerations, and intracranial hemorrhage.Intraventricular hemorrhage included grades I, II, and III hemorrhage.“Other injury to scalp” category of birth trauma included cephalohematoma, caput succedaneum, epicranial hemorrhage, and lesions of the scalp.Several other types of traumata were analyzed, including skull fracture, fracture of clavicle, long bones, injury to brachial plexus, hematoma or rupture of the spleen, hematoma or rupture of the liver, injury, or damage to the eye(s), facial injury, fetal laceration by scalpel, ecchymosis, and subcutaneous adiponecrosis.Other birth injuries analyzed as individual outcomes included hypoxia and asphyxia at birth; intrapartum and peripartum fetal death.Apgar scores and 5 and 10 minutes were divided in two categories: ≤7 and > 7.2 concentration in umbilical cord <22mEq/L; birth asphyxia, arterial pH <7.0; APGAR score less than 3 at 5 and 10 min, signs of hypoxic ischemic encephalopathy, evidence of multi-organ suffering.The outcome variables that assessed fetal birth trauma were defined as follows: hypoxia, OThe main outcome of this study was trauma at birth which included intracranial laceration and haemorrhage, injuries to scalp, injuries to central and peripheral nervous system, fractures to skeleton, and facial and eye injury.upplementary material A). In order to better assess the overall impact of mode of birth on the newborn outcomes in term and preterm deliveries, we merged all types of birth trauma and created a new variable, “all birth trauma”. Mother and newborn days of hospitalisation, and the risk of admission to neonatal intensive care unit (NICU) were also assessed.The secondary outcomes included intrauterine hypoxia, birth asphyxia, neonatal aspiration syndromes and neonatal death, subcutaneous adiponecrosis, ecchymosis, fetal laceration by scalpel. ICD-10 codes used for specific diagnoses are listed in Appendix  ± standard deviation (SD). Categorical variables were presented as proportions.Bivariate analysis was performed to examine the associations between the mode of birth, demographic characteristics and clinical outcomes in term and preterm pregnancies. Chi square test was used for categorical variables and ANOVA for continuous variables, as appropriate.Multivariate logistic regressions assessed the association between mode of delivery and birth trauma in term and preterm pregnancies adjusting for potential confounding variables. Term pregnancy and delivery by CS were the reference categories. Confounding factors that remained in the multivariable models and were adjusted for included maternal demographic and clinical characteristics  maternal pre-existing pathology , and pregnancy complications .Statistical analysis was conducted using SPSS statistical software, version 20 for Windows. Where appropriate unadjusted (OR) and adjusted odds ratio (aOR) and their 95% confidence intervals (CI) were computed; a nominal P-value of less than 0.05 was considered statistically significant.The study was approved by the ethical committee of “Cuza-Voda” University Hospital, No 2052/16.02.2021 and “Gr T Popa” University of Medicine and Pharmacy, No 101/08.07.2021 Iasi, Romania, and was performed in line with the Declaration of Helsinki.Signed informed consent from patients was not required for this retrospective study that used a denominated data set for secondary data analysis. All patients admitted to hospital provided informed written consent to have data from their anonymized medical records used in research as pooled data.From 67,348 women who delivered at our institution between January 2007 and December 2017, 62,330 women met the criteria of inclusion in the study. From these, 6,794 (10.9%) were preterm deliveries. Among women included in the study, 28,191(45.2%) were delivered by CS and 34,139 (54.8%) had a spontaneous vaginal delivery. Approximately 63% of women who delivered by CS were primiparous. Baseline demographic and clinical characteristics of the study population are presented in As shown in Duration of maternal hospitalization was longer in women with CS delivery. There was three days difference for moderate and late preterm deliveries in women delivered by CS compared to VD  and less, of only one day, in term deliveries . In terms of neonatal days of hospitalization, there was no significant differences between VD and CS for both preterm and term babies.We observed a slightly higher incidence of NICU admission for very preterm deliveries after CS comparing with VD , as well for moderate to late preterm . Concerning term deliveries, 1.3% were admitted in NICU after CS vs 0.9% in VD . After adjusting for maternal clinical characteristics, CS delivery continued to be associated with increased odds of admission to NICU. In our study, admission in NICU was longer among CS group, except for the extremely preterm babies, were the admission period in NICU was similar between CD and VD . The median duration of admission in NICU remained increased for both CS and VD in the adjusted model for confounding variables.For all extreme preterm babies, the Apgar score at 5 min was ≤7. For the preterm births in 28–31 weeks and 32–36 weeks groups, there were no significant differences in Apgar scores at 5 min between VD and CS group. For term pregnancy, Apgar score ≤7 at 5 min was more frequent for VD , whereas Apgar score >7 at 5 min was more common in CS than VD ; the findings remained similar in the adjusted models.Fetal hypoxia was more common for VD route of delivery compared to CS . After adjusting for confounders, the odds of neonatal hypoxia after VD decreased from 39% to 19.7% compared to those delivered by CS . There was no significant difference in the risk of developing severe asphyxia between VD and CS delivery. Stillbirth babies were more likely to be delivered vaginally, regardless of the gestational age.other scalp injury” birth trauma category, that included all minor injuries, accounted for the majority of all birth trauma . When comparing CS to VD, and term to preterm deliveries, odd ratios of all birth scalp traumas were higher for VD  and term deliveries .There were no significant differences in the rates of cranial traumatic haemorrhage  in term and preterm neonates between CS and VD. The “The occurrence rates of intraventricular haemorrhage were similar among VD and CS groups, when stratified by gestational age of delivery groups. Only one case of cranial nerve lesion was identified, and this was a term newborn. Regarding fractures at birth, the majority of clavicle fractures were recorded for term births , fewer cases for the 32–36 weeks group, and only one case for very low preterm. For moderate to late preterm group, after adjusting for maternal clinical characteristics, VD continued to be associated with increased odds (9.2 vs 4.2) of fracture of clavicle. Brachial plexus injury was more frequent in term births (42 vs 4 cases) compared to preterm births, and for VD compared to CS .Eye injury due to trauma at birth  were more frequent for term neonates delivered vaginally . There was no difference in fetal facial laceration in VD and CS for all delivery age groups.Meconium aspiration syndrome was reported in late preterm and term deliveries. Among term neonates, there was a 70.6% to 29.4%  difference between VD and CS. Subcutaneous fat necrosis of the newborn was more common after CS, in full-term and late preterm births. Ecchymoses were more common in term compared to preterm deliveries , and after VD compared to CS .The aim of the current study was two-fold, to assess the incidence and characteristics of birth trauma in units from our country, and to contribute to the existing literature on perinatal trauma, thus strengthening the quality of evidence in support of clinical protocols and guidelines worldwide regarding the safest mode of delivery in preterm pregnancies, with fetuses in vertex presentation. In spite of recent research accruing data on the optimal mode of delivery for preterm and very preterm infants, there is still not enough information to provide clear guidance on the chosen method of birth in preterm pregnancies and a consensus has not been yet achieved .Because a RCT was not proven to be feasible, the evidence on birth trauma is based mostly on retrospective studies. Therefore, we conducted a retrospective study on a large population of 62,323 women that compared neonatal birth injuries in term and preterm births, in vaginal versus caesarean delivery. The most important findings of our study are as follow: i) the incidence of birth trauma was 16.2 per 1000 births; ii) there is an increasing trend of delivery of preterm babies by CS ; iii) the incidence of trauma at birth is higher after 28 weeks gestation, in VD compared to delivery by CS; iv) preterm babies are not a higher risk of major birth trauma if they are delivered vaginally compared to delivery by CS; v) there was no difference in the incidence of birth trauma before 28 weeks gestation in babies delivered vaginally or by CS.When we stratified by type of birth trauma we observed that: i) there was no significant difference for minor trauma between preterm and term infants delivered either by CS or VD; ii) fetal birth hypoxia was more common in term babies delivered by CS, whereas asphyxia was more common in preterm birth delivered by CS; iii) low Apgar scores were more common in late preterm delivered by CS and term babies delivered vaginally; iv) there was difference in duration of hospitalization of mothers between CS and VD, but not in the duration of hospitalization of the newborns.The total rate of CS in our study was 45.2%, which is a high incidence compared to other European countries (i.e.22% in Belgium) . Recent Although, CS is safer today and it is now commonly performed to protect the fetus, newborn morbidity and mortality still do exist . A cohorThere are several factors that may help explaining the high rates of delivery by CS among present cohort of preterm and term neonates. Along with the fear of malpractice, lesser experience of young obstetricians in instrumental deliveries, increased usage of epidural analgesia during labor, an increased desire of women for CS delivery is noted among our obstetrical population. It is also important to mention that the center where the study was conducted is a level 3 maternity hospital and a referral center for higher risks pregnancies and women with comorbidities. In addition, in Romania, the induction of labour with prostaglandins is not part of labour management guidelines, thus leading to higher incidence of caesarean births.In our cohort, the rate of preterm birth was 10.9% and that of birth trauma 16.2%. Our reporting included all types and degrees of severity of birth trauma and injuries. The rate of birth trauma reported by others was about 2% in normal VD in cephalic presentation and 1.1% in CS, but included only selective reporting of various types of birth trauma .Some studies have shown lower risk of birth trauma for CS delivery , 18, 19.Compared to other studies, we found a higher rate of overall birth injuries. If we were to exclude the most common minor injuries that represented 75% of all injuries, the calculated incidence rate of birth trauma would have become 40.55 per 1000 births , index similar with that reported by other studies. Major traumas were rare and no statistically significant differences was seen between VD and CS. This is an agreement with the findings reported by a Cochrane systematic review on the outcomes of birth in preterm infants which reported a risk ratio of 0.56, with a 95% CI of 0.05 to 5.62 for infant birth injury when comparing planned immediate CS and planned VD in preterm births [We report no difference in our study in the incidence of intracranial lacerations and cranial traumatic haemorrhage  in preterm pregnancies delivered either by CS or VD at any gestational age. Previous studies have produced conflicting results, with some suggesting a protective effect of CS delivery, , 9, 21 wNerve injuries were rare, with brachial plexus injury being most common. In this study we observed an increase in this type on injury with gestational age, with the majority of these type of injury occurring after 36 weeks gestation, and almost three times more frequent in VD delivery. Others report similar findings, with CS being protective of nerve injury .The main limitation of our study is the retrospective design. The data was retrieved from electronic and handwritten patient records. The data is stored in the electronic records based on administrative criteria, which inevitably led to unavailability of some desirable information or misclassification. There was no data available on the induction of labour or detailed circumstances leading to decision on CS delivery. Furthermore, we used the most recent ICD classification, ICD 10, although it is possible that misclassification may have occurred due to use previous ICD codes in years preceding our study.Not reporting on mortality rates was another limitation of our study. We did report, however, on the rate of stillbirth, that was 0.67% in our study, comparable to previous reports , 25.This study has several strengths. We have evaluated the impact of VD and CS delivery in a large sample of term and preterm pregnancies. Additionally, the database used combined maternal and neonatal information, allowing us to ensure the accuracy of data collected. Furthermore, the importance of this study is two-fold. Firstly, to date, there are no other studies conducted in Romania to assess the rate and consequences of birth trauma at national level. This study conducted in one the largest tertiary maternity center in the country is representative and can be generalised to the entire population of the country. This is more significant if considered that Romania is the country with highest incidence of premature births, of about 10–12%, and one of the highest incidences of CS (from 34% in 2014 to exceeding 60% in 2018) in Europe. Thus, it is important to understand the causes driving this increase, being these supported by clinical evidence or driven solely by fear of mass media and medical error with consequent reprimand and liability. Secondly, our analysis of mode of delivery aligns with the trend observed worldwide in assistance at delivery, with a dramatic increase in the rates of CS and decrease in instrumental deliveries, driven mostly by socio-economic factors. The rate of instrumental delivery, less than 1% in our centre, allowed us to exclude these women from the analyses, while enabling comparison of VD and CS and estimation of birth trauma without the bias of trauma by forceps and vacuum. Thirdly, vacuum assisted vaginal delivery is contraindicated in pregnancies less than 34 weeks gestational age or estimated fetal weight lower than 2500 gm.In summary, our study does not support benefits of CS over VD for premature newborns in order to avoid major birth trauma. Therefore, we advise the decision on the method of delivery of preterm babies based on obstetric indications, while considering the benefits and urgency of fetal delivery. Although the incidence of total birth trauma favor CS delivery, severe birth trauma develops equally frequent in CS and VD for preterm babies in vertex presentation. This led to the conclusion that overall, the evidence to date remains controversial and, therefore, prospective studies are needed to explore whether CS in preterm births protects against birth trauma. Pending future studies, these findings suggest that CS does not further protect the singleton premature newborn in cephalic presentation from major trauma and that VD can be considered.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Many factors can affect the clinical outcome of extremely premature infants (EPIs), but the effect of sex is paradoxical. This study used propensity score matching to adjust baseline information to reassess the clinical outcome of EPIs based on sex.A retrospective analysis was performed on EPIs admitted in the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from 2011 to 2020. A propensity score matching (PSM) analysis was used to adjust the confounding factors including gestational age, birth weight, 1-minute Apgar score ≤ 3, withholding or withdrawing life-sustaining treatment(WWLST), mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. The survival rate at discharge and the incidence of major complications were evaluated between the male and female groups.P>0.05). However, the incidence of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and moderate to severe BPD in the male group was significantly increased , especially at birth weight between 750 and 999 grams.A total of 439 EPIs were included, and 240 (54.7%) infants were males. After matching the nine confounding factors, 148 pairs of infants were finally enrolled. There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups (all The male EPIs have a higher risk of respiratory complications than females, particularly at 750 to 999 grams of birth weight. Gestational age (GA), birth weight (BW), antenatal steroids administration, active resuscitation, maternal age, and hypertensive disorders of pregnancy are considered to impact the outcomes of preterm infants –6. ThereHowever, the male disadvantage appears to be uncertain in extremely preterm infants  or/and very preterm infants . Binet et al. found that there was no significant difference in survival rate between male and female EPI . And simThe main reason for the above conflicting results may be relative to the inconsistent baselines of the study subjects. Some characteristics such as GA, BW, and antenatal steroids, are quite different between the male and female groups, which have important impacts on mortality and morbidity in EPIs/VPIs. So, in this study, the propensity score matching method was used to adjust the baseline characteristics to estimate the impact of sex on the clinical outcome of EPIs. Furthermore, given that GA and BW were the most important factors influencing EPIs outcomes, we performed subgroup analyses of sex differences according to GA and BW classification.in vitro fertilization (IVF), delivery method, 1- and 5-minute Apgar score, mechanical ventilation, the survival rate at discharge, and the major complications during hospitalization; (2) maternal data: age at delivery, antenatal steroid administration, and the major pregnancy complications.The EPIs who were admitted to the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from January 1, 2011, to December 31, 2020, were selected as the research subjects. The exclusion criteria were as follows: (1) incomplete data of the infant or mother; (2) various serious congenital malformations, such as genetic metabolic diseases, central nervous system malformations, and cardiovascular malformations. The selected EPIs were divided into male and female groups, and then stratified by GA and BW, namely gestational age <26 weeks, 26 weeks, and 27 weeks, birth weight <750g, 750-999g, and ≥1000g. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University. The following neonatal and maternal data were collected: (1) neonatal data: sex, GA, BW, twin/multiple pregnancy, Survivors were defined as EPIs who survived at discharge . NeonataP<0.05 was considered statistically significant.All data were analyzed using SPSS 26.0 software . We initiated a 1:1 matched analysis by PSM with a nearest-neighbor matching algorithm to adjust the baseline characteristic differences between the two groups, including GA, BW, 1-minute Apgar score ≤ 3, WWLST, mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. These covariates were selected based on the reported studies and our data, which were found to be relative to the mortality and morbidity of preterm infants –30. We uFrom 1 Jan 2011 to 31 Dec 2020, there were 445 EPI admitted to the Department of Neonatology, the Third Affiliated Hospital of Guangzhou Medical University. 3(0.67%), 1(0.22%), and 2(0.45%) infants were excluded due to incomplete data, genetic metabolic diseases, and the presence of congenital anomalies, respectively. At last, a total of 439 EPIs were enrolled and were divided into male or female groups. Before matching, there were 240 male infants and 199 female infants. After matching, each group included 148 infants. The baseline characteristics of the two groups before and after matching are shown in P>0.05). The incidence of RDS and BPD in the male group was significantly higher than that in the female group before and after matching . But the difference in the incidence of moderate to severe BPD between the two groups was just found after matching , not before matching (P>0.05). On the contrary, the incidence of IVH in the male group was significantly higher than that in the female group before matching , but not after matching (P>0.05). There was no significant difference in the incidence of severe IVH, PVL, NEC, ROP, HAI, or treated PDA between the two groups before or after matching. See There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups after matching ; and so did the incidence of moderate to severe BPD . On the other hand, the male infants in the subgroup with birth weight of 750 to 999 g, had higher incidences of RDS and BDP than female infants before or after matching . More interestingly, the higher incidence of moderate to severe BPD in male infants was just seen after matching , not before matching. In the other GA and BW subgroups, the incidence of RDS, BPD, and moderate to severe BPD between male and female infants were not significantly different before or after matching , as shown in In the subgroup analysis, the male infants in the subgroup with 27 weeks of gestation had an increased incidence of BPD after matching, when compared with the female infants , Guangzhou Science and Technology Project , Medical Science and Technology Research Fund Project of Guangdong Province , and Guangdong Science and Technology Plan Project .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.


Arachnoid cyst is a neurological tumor. It’s rare and benign. Its association to psychosis has been described in literature.Through a case report and a review of the literature we hypothesize that arachnoid cyst is the cause of resistance in a patient with schizoaffective disorder.Starting from a case report, we conducted a literature review on “PubMed”, using key words “arachnoid cyst”, “arachnoid cyst a psychiatry”, “arachnoid cyst and schizoaffective disorder”, “arachnoid cyst and schizophrenia”Mr. AA is 50 years old, has diabetes treated with metformin, hypercholesterolemia and celiac disease under gluten free diet. He has been diagnosed with schizoaffective disorder in 1992, initially put on haloperidol and carbamazepine. Since the patient wasn’t getting better, we suspected no-compliance so we switched haloperidol for fluphenazine decanoate. The patient still suffered from persecutory delusion and auditory hallucinations. We started him on clozapine still with no improvement. So, we concluded to the resistance of schizoaffective disorder considered electroconvulsive therapy (ECT). A cerebral MRI was conducted, prior to ECT, objectifying a left anterior frontal arachnoid cyst of 26 millimeters from the main axis producing a mass effect on the cerebral cortex. This neurological tumor didn’t require neurosurgery.Our patient was resistant to all treatments including clozapine. The only anomaly discovered was the arachnoid cyst. Could this explain the resistance of this patient and others like him? Could this be an interesting research path to further elucidate the mystery of metal disorder?No significant relationships.


Low birth weight (LBW) is defined as a birth weight less than 2500 g. It is an important predictor of early neonatal mortality, morbidity, and long-term health outcomes. The aim of this study was to identify risk factors for low birth weight in Marrakech Morocco.A retrospective based case-control study was conducted from July 2018 to July 2019. 462 mother infant pairs  were included in the study. Data were collected through face to face interview using a structured and pretested questionnaire. The collected data were managed with Statistical Package for Social Science (SPSS) version 20. Bivariate and multivariate binary logistic regression were used to identify factors associated with low birth weight at p-value < 0.05 with their respective odds ratios and 95% confidence interval.The univariate analysis revealed the effect of the following determinants on the LBW: rural residence, father’s age, father’s professional activity, consanguinity, family type, mother’s low educational level, and mother’s intense physical activity. After the multivariate analysis, the risk factors identified were: rural residence (P = 0.017), father’s professional activity (temporarily working) (P = 0.000), absence of the consanguinity link (P = 0.016), and mother’s intense physical activity (P = 0.014).Results show father’s professional activity (temporarily working), rural residence, absence of the consanguinity link and mother’s intense physical activity are independent predictors of low birth weight. The current findings add substantially to the growing literature on the influence of parent’s socio-demographic and cultural factors on LBW in resource-constrained settings and provide empirical data for public health interventions to reduce low birth weight. Low birth weight (LBW), defined as a birth weight less than 2500g, is a significant risk of death and disability . WorldwiGlobally, an estimated 15% to 20% of all births are LBW , 5. The In fact, the goal of the organization is that by the year 2025 the number of children born weighing less than 2500 g will have been reduced by 30% , which cIn developing countries, the low birth weight rate is twice as high than in developed countries with 16.5% against 7%. Despite progress in socio-economic and health care in recent decades, the proportion of low birth weight infants is still high, and is even increasing in some countries .A systematic review of low birth weight in Africa showed an increased risk of death, growth retardation and delayed neurodevelopment among very low birth weight and extremely low birth weight children .Additionally, low birth weight is associated with a risk of hypertension later in life . Many deIn other studies, educational level and occupational status , maternaOn the other hand, multiple micronutrient supplements and preventive antimalarial drugs during pregnancy had a positive effect on low birth weight , 22. IdeA retrospective case-control study was conducted from July 2018 to July 2019, at the maternity hospital of Ibn Zohr Hospital, Mother and Child Hospital CHU Mohammed VI; and at three health centers with a delivery module: Loudaya; Massera and Syba in Marrakech. These maternities recorded a very high number of deliveries. According to the statistics provided by the Health Delegation of the Marrakech-Safi Region, the total number of live newborns in 2017, at the CHU, was 14932 . Ibn Zohr Hospital and CHU Mohammed VI ensure 83% of deliveries in this region. The health services offered by these two establishments include prenatal consultations and postnatal monitoring of newborns.2. The region includes 215 municipalities-divided into 18 urban and 197 rural. The capital of the region is the province of Marrakech.The region of Marrakech-Safi covers an area of 41,404 km2 or 6% of the national territory and has 4520569 inhabitants . The density of 109 inhabitants per kmNewborns who were born in the two public hospitals and three health centers during the study period (12 months) were included in this study. Live newborns delivered at term without known risk factors (i.e. intrauterine growth restriction) of low birth weight were included in the study. Mothers with premature delivery (before 37 completed weeks of gestation) and mothers with medical status that would affect birth weight , were excluded from the study. Mothers who gave birth to neonates weighing less than 2500 grams were cases and neonates’ ≥2500 grams were controls.The outcome/dependent variable was low birth weight. The exposure/independent variables were socio-economic and cultural variables .The Sample size was calculated using the STATCALC program of EPI6, for unmatched case control with 95% confidence and 80% power to detect a minimum odds ratio of 2.0 assuming that the least prevalent factor will be present in minimum 10% of the controls as reported by Anand13 in his study. The final calculated sample size was 231 cases and 231 controls.Both cases and controls were recruited on an ongoing basis until the required sample size was fulfilled.The hospitals and the health centers where the study takes out were selected purposely. Cases (birth weight less than 2500 grams) were included in the study and two consecutive mothers in the controls (birth weight ≥2500 grams) were interviewed. Data for the study were extracted from birth registers containing information about maternal and newborn characteristics using a structured database. Data were collected using a pre-tested and structured questionnaire through a face-to-face interview. The questionnaire includes information about: Socio-economic and cultural characteristics of mothers, Socio-economic and cultural characteristics of father’s, and characteristics of birth. The questionnaire was validated and pre-tested on 5% of the sample size in Mother and Child Hospital CHU Mohammed VI. The data was collected during two day at each hospital and one day at each health centers. Supervisors checked the completeness of the data.The statistical package for social sciences (SPSS) version 20.0-computer software was used for statistical analysis. Frequency distributions and cross tabulation between cases and controls were completed. Univariable and multivariable logistic regression analyses were computed in order to understand the effect of independent variables on the outcome variable.The variables with p-value ≤0.2 in the univariate analysis were introduced into multivariable logistic regression analysis. Backward stepwise logistic regression method was used the Hosmer-Lemeshow test was used to assess goodness-of-fit. We considered p-value < 0.05 as level of significance.Official authorizations were obtained from the Regional Delegation of the Ministry of Health in Marrakech and from the Directorate of the Hospitals to access the maternity services and conduct this study. Informed verbal consent was obtained from study participants after being made informed of the objectives of the study. Confidentiality was guaranteed by keeping the anonymity of the respondents.The weight of all newborns ranges from 700g to 5000g and the mean is 2594.94g (standard deviation (SD) = 939.27g).The boy/girl sex ratio was 1.22.The mean weight of newborns is 1806.86g (SD = 529.42) in LBW cases, and 3383.01g (SD = 490.38) in Control cases.A higher proportion of cases belonged to extended families (58.9%) than controls (44.2%). The difference was statistically significant (p = 0.002).We identified in a first step the factors associated with LBW, then we performed a multivariate logistic modeling . The varFor the case, the weight of newborns varies from 700g to 2400g with an average of 1806.86g (SD = 529.42g), while for the controls, the weight of newborns varies from 2500g to 5000g with an average of 3383.01g (SD = 490.38g).This calculated average value is lower than those found by Amor (1989) , Baali  did not find any relationship between maternal age and fetal growth . Afeke . Of all the studies reviewed, only two found that paternal age was also associated with a high probability of LBW .We also noticed that living in rural areas was significantly associated with LBW . The same finding was reported by Abubakari (2015) in a study conducted in Ghana . Other sIn addition, the univariate analysis in this study highlighted the fact that low maternal education was strongly associated with LBW (p = 0.000). Without doubt, when mothers are highly educated, they attain improved nutritional status, health-seeking behaviors, and better maternal experiences with pregnancy and childcare. Furthermore, for those women, sexual initiation or increased contraceptive use to avoid pregnancy are obviously delayed , 36. TheThe mother’s professional activity is not significantly associated with LBW (P = 0.360). Indeed, we found that the majority of mothers were jobless (housewives 98.3%). However, Al-dabbagh , noted tIn this study, a higher proportion of cases had fathers who were unemployed or temporarily working (39%) than in the control group (6.9%), this difference was significantly related to LBW .Moreover, the absence of inbreeding between spouses are significantly connected with LBW  similarly to the results found in many studies –40.In the present study, a higher proportion of cases belonged to extended families (58.9%) than controls (44.2%). Similar to this, Vijayalaxmi in her study conducted in urban area of Bangalore found that majority of the women who delivered LBW babies were living in joint families (54.0%) .Additionally, we noticed a positive association between high physical activity of the rural mother and LBW . According to Laura , workersWhat is more, active smoking is almost absent among the mothers in our study while passive smoking is not a determinant cause for low birth weight. Vahdaninia , noted iThis study showed that Socio-economic and cultural characteristics were risk factors for low birth weight in the study areas. Residence, low professional activity of the fathers (temporarily working), consanguinity link and maternal physical activity were significantly associated with low birth weight. These findings contribute to the growing literature on the influence of maternal and paternal socio- economic and cultural factors on LBW in resource-constrained settings. Additionally, efforts should be done to improve living standard and lifestyles of mothers. Community based studies are needed to better address household and socio-economic factors with observation.S1 File(SAV)Click here for additional data file.


The multicountry Women First trial demonstrated that nutritional supplementation initiated prior to conception (arm 1) or early pregnancy (arm 2) and continued until delivery resulted in significantly greater length at birth and 6 mo compared with infants in the control arm (arm 3).We evaluated intervention effects on infants’ longitudinal growth trajectory from birth through 24 mo and identified predictors of length status and stunting at 24 mo.clinicaltrials.gov as NCT01883193), which was conducted in low-resource settings: Democratic Republic of Congo, Guatemala, India, and Pakistan. Longitudinal models evaluated intervention effects on infants’ growth trajectory from birth to 24 mo, with additional modeling used to identify adjusted predictors for growth trajectories and outcomes at 24 mo.Infants’ anthropometry was obtained at 6, 12, 18, and 24 mo after the Women First trial (registered at z-score (LAZ) trajectory, treatment arm was a significant predictor, with adjusted mean differences of 0.19 SD  and 0.17 SD  for arms 1 and 2, respectively. The strongest predictors of LAZ at 24 mo were birth LAZ <–2 and <–1 to ≥–2, with adjusted mean differences of –0.76 SD  and –0.47 SD , respectively. For infants with ultrasound-determined gestational age (n = 1329), the strongest predictors of stunting were birth LAZ <–2 and <–1 to ≥– 2: adjusted relative risk of 1.62  and 1.46 , respectively.Data for 2337  infants were evaluated. At 24 mo, stunting rates were 62.8%, 64.8%, and 66.3% for arms 1, 2, and 3, respectively (NS). For the length-for-age Substantial improvements in postnatal growth are likely to depend on improved intrauterine growth, especially during early pregnancy. Rates of stunting at birth, low birth weight, and small for gestational age were also significantly reduced in the intervention arms compared with a nonintervention control group . DespiteThe potential for persistence of such preconception and prenatal effects on linear growth faltering during the complementary feeding period, that is, over the second half of the 1000 d, is less clear. Although declining, the overall prevalence of stunting in children <5 y of age remains in the 20–25% range, with rates varying substantially among regions of the globe . A recen1) to examine postnatal growth and whether the benefits of the intervention evident at birth and 6 mo were detectable through the first 24 mo after birth, 2) to identify predictors of the longitudinal growth trajectory from birth through 24 mo of age, and 3) to identify, in a cross-sectional analysis, the major predictors of linear growth status at 24 mo for infants of all participating women and separately for the subgroup of infants for whom gestational age determinations were available.Thus, the goal of the analyses in this report was to determine whether the benefits of improved maternal nutritional status prior to conception and during early gestation on fetal and early postnatal growth were sustained at 2 y. The objectives of these analyses were 3-fold: This analysis included prospectively obtained anthropometry of those live-born infants of the women in the WF trial  who had birth measurements and who consented to the follow-up growth monitoring study at 6 mo and continued through 24 mo postnatal age. Growth from birth to 6 mo was an a priori secondary outcome of the primary trial, and results have been reported elsewhere  at the time of randomization with continuation for at least 3 mo prior to conception through to delivery (arm 1), initiation of the same supplement late in the first trimester of pregnancy and continued through to delivery (arm 2), or receipt of no trial supplement (arm 3). Women in arm 1 and arm 2 (once having started the primary supplement) who were underweight or had inadequate gestational weight gain were provided an extra protein-energy supplement until delivery. More than 85% of the participating women in 3 of the sites received the protein-energy supplement; <10% of the Guatemalan women qualified for the second supplement. The trial was conducted in low-resource, rural, and small city settings in 4 countries: Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan , prematurity], we examined potential predictors from the subgroup of infants for whom gestational age was determined by first-trimester ultrasounds; ultrasound capacity was not available in the DRC.The central data coordinating center  created the randomization scheme for the original trial, generating the allocation sequence separately for each research site. To ensure geographic balance, a permuted block design stratified by geographical clusters was used to generate the randomization sequence for assigning individual participants to a trial arm. The allocation ratio was 1:1:1 within blocks, which randomly varied between sizes of 3, 6, or 9. At each site, once the responsible home visitor research assistant (HVRA) identified an eligible participant, the HVRA then received the randomization assignment from their site-specific data manager, who generated the randomization assignment from the centralized computerized data management system maintained by the DCC.z-scores, which accounted for sex and age at the time of measurement, were calculated for length-for-age z-score (LAZ), weight-for-age z-score (WAZ), weight-for-length z-score (WLZ), and head circumference-for-age z-score from the WHO Child Growth Standards ; nonstretch, plasticized measuring tapes ; and length boards accurate to 1 mm . The tandards . For womhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000057/. Throughout the intervention phase of the trial, a data monitoring committee designated by the Eunice Kennedy Shriver National Institute of Child Health and Human Development monitored the safety of the trial. Adverse events that were monitored included pregnancy outcomes, adverse neonatal events, hospitalizations, and allergic reactions ; and the DCC . Written informed consent was obtained from all participants. The study protocol is available online: eactions , 8.R2 and comparisons of log-likelihoods were also considered for final model selection. In addition, interactions between arm and site, sex and arm, and arm and parity were examined.For all the adjusted models, collinearity of independent variables was examined using Spearman and Pearson correlation coefficients for discrete and continuous variables, respectively. In addition to reviewing the correlations, 2) was categorized as ≤24, >24, and missing.Some of the continuous predictors (height and BMI) were categorized based on the cutoff values identified by classification and the regression tree algorithm. Paternal variables were missing for ∼15.5% infants. A separate category for the missing values was created to include these records in all the final models. Paternal height was categorized as a 3-group variable: ≤160 cm, >160 cm, and missing. Similarly, paternal BMI .Two-sided After excluding biologically implausible anthropometric measurements (length and head circumference) according to WHO guidelines, the longitudinal analysis included all live-born infants with birth length measurements obtained by 7 d of age who were alive at 6 mo and whose parents had provided consent for follow-up to 2 y. We constructed longitudinal models using generalized estimating equations (GEEs) to examine whether the trajectory of growth for study infants from birth through 24 mo age differed by treatment arms. Baseline maternal characteristics that differed across the 3 treatment arms, or between infants included or excluded from the analysis due to missing data, were considered for inclusion as covariates in these models: socioeconomic status (SES), maternal education, parity, BMI, height, and stunting. Model selection approaches described above were used to develop the final model. Continuous (binary) outcomes assumed a normal  distribution with identity (log) link and an autoregressive correlation structure with robust sandwich estimator  to account for infant repeated measures over time. We examined treatment heterogeneity by country using interaction terms for arm and country. Interactions were also examined to assess the stability of treatment effects over time for each model.A second series of longitudinal GEE models were fit on the same data to identify the predictors of the longitudinal growth trajectory from birth through 24 mo, adjusting for treatment arm. These models also adjusted for maternal and paternal BMI and height. In addition, interactions between arm and site, arm and visit, sex and arm, and arm and parity were examined and included in the final model, as appropriate.We used cross-sectional analyses, linear (robust Poisson) regression for continuous (binary) outcomes, to identify the major predictors of linear growth status at 24 mo. First, for the all-site analysis, the following potential predictors were considered: SES; maternal education, parity, stunting, height, and BMI; paternal height and BMI; and birth measurements of length, LAZ, and stunting, categorized as none (LAZ ≥–1), mild (LAZ <–1 to ≥–2), or moderate (LAZ <–2), and weight, WAZ, WAZ <–2, weight-for-length, WLZ, WLZ <–2, sex, and low birth weight (LBW) using WHO growth standards. After model selection, the final models included arm; site; cluster; interaction between site and cluster; SES; maternal education, parity, BMI (≤22 and >22), and height ; and paternal BMI  and height .z-scores derived from INTERGROWTH-21st (IG) fetal growth charts , mild (LAZIG <–1 to ≥– 2), or moderate (LAZIG <–2); weight; WAZIG; WAZIG <–2; weight-for-length; WLZIG; WLZIG <–2; SGA; preterm birth (<37 wk of gestation); and sex. All these predictors were considered in the adjusted models for each outcome variable. Upon model selection, the final models included arm; site; cluster; interaction between site and cluster; SES; maternal education, parity, BMI (≤22 and >22), and height ; paternal BMI  and height ; infant sex; birth stunting categories; preterm birth; and SGA (not LBW).Separate analyses were conducted for the set of data from India, Pakistan, and Guatemala with available gestational age determined by first-trimester ultrasound. The predictors considered were SES; maternal education, parity, stunting, height, and BMI; paternal height and BMI; and birth measurement h charts  of lengtSupplemental Figure 1). Baseline characteristics for the mothers and fathers of the infants and young children of the present analyses are presented in This analysis is based on infants born to 2324 women who participated in the primary WF trial and consented to the follow-up study, for which enrollment and randomization occurred between December 2013 to October 2014 . BaselinSupplemental Table 1. After only modest decline in mean LAZ from birth through 6 mo, the mean LAZ for all arms declined sharply between 6 and 12 mo, with further decline between 12 and 24 mo .Means (SDs) of unadjusted anthropometry at 0, 6, 12, and 24 mo and pairwise comparisons among arms are presented in Supplemental Table 2), with arm 1 performing better than arms 2 and 3 for both length and LAZ. No other site-specific comparisons among arms demonstrated statistically significant differences for linear growth (P = 0.0281), WAZ (P = 0.0077), and WLZ (P = 0.0337). Separate models that included the interaction effects between arm and time of visit generally demonstrated attenuation of the treatment effects over time .In the adjusted longitudinal models, significant interactions indicating treatment heterogeneity by site were observed for length and LAZ, and site-specific adjusted models were thus used for these 2 outcomes. Significant treatment effects on linear growth were observed only in the DRC , with arDetermination of demographic predictors of the longitudinal growth trajectory from birth through 24 mo (regardless of any interactions) was the second major objective of this analysis. For LAZ, the strongest predictor was maternal height >150 cm (adjusted mean difference 0.54 SD), followed by paternal height >160 cm, maternal education (secondary), parity ≥1, and male infant sex (negative adjusted mean difference). Treatment arm was a significant predictor of linear growth trajectory, with greater mean difference for both arms 1 and 2 compared with arm 3 .R2 = 0.340). Predictors of stunting, expressed as adjusted RR, included birth LAZ, with both mild and moderate stunting at birth associated with an adjusted RR of 1.38. Maternal height (>150 cm) was associated with an adjusted RR of 0.73; other significant predictors were similar to those for LAZ  was associated with adjusted mean difference of +0.45 SD. , LBW, an for LAZ . CorrelaIG <–2 and <–1 to ≥–2), each associated with significant and negative adjusted mean differences of –1.12 SD and –0.51 SD, respectively; preterm birth was associated with an adjusted mean difference of −0.48 SD. Maternal and paternal heights  were negatively associated, whereas maternal BMI, maternal education (secondary), and SES were positively associated with adjusted mean differences (model R2 = 0.432)  . Low par= 0.432) . CorrelaThe most striking findings of the present analysis of growth status at 2 y of the children of participants in the WF trial were the severe stunting rates; evidence of persistence of a treatment effect on longitudinal linear growth for the preconception arm, which was driven predominantly by one site (DRC); that both maternal and paternal heights were the strongest predictors of longitudinal linear growth trajectory; and that deficits in birth length were the strongest predictors of attained LAZ and of stunting at 2 y. With no postnatal intervention, infants in both maternal intervention arms experienced a steep decline in LAZ between 6 and 12 mo and a slower but steady downward progression thereafter. Mild and moderate stunting at birth were associated with 0.5 to 1.0 lower adjusted mean difference in LAZ and a 40–60% increase in stunting risk at 2 y. Thus, despite the overall pattern of linear growth faltering for the offspring of mothers in all arms of the primary trial  and intervention arm of the primary trial as significant predictors. However, with inclusion of birth length in the cross-sectional analysis at 24 mo, the intervention arm was no longer significant, and birth length outcomes were the strongest predictors of lower LAZ and risk of stunting; for the group of infants with gestational age determinations, moderate stunting at birth had the highest risk of stunting at 24 mo. Low birth weight (but not SGA) was a significant predictor but had a considerably smaller impact on the adjusted mean difference in LAZ at 24 mo compared with those associated with the deficits in birth length, supporting the premise that very early fetal growth may program longer-term linear growth , 25. OurP = 0.03) placental area than the control arm, and placental area was correlated with LAZ at birth  of offspring of the WF trial participants who contributed to the data through 24 mo and supported a rigorous analysis of longitudinal postnatal growth. The multicountry design of the original randomized trial is a strength. Although the results reflect heterogeneous settings and participants, these features also support generalizability of the findings. Limitations include the availability of first-trimester gestational age dating from only 3 of the 4 sites and the absence of data on postnatal morbidity and biochemical indicators of inflammatory, metabolic, and nutritional status that could potentially have provided insights into factors driving the linear growth faltering we observed. However, given the strength of the predictive variables and their consistency with observations from the literature, we submit that the impact of such postnatal factors is unlikely to have substantially attenuated the findings.In summary, the sharp downward trajectory of linear growth after 6 mo of age and the profound stunting rates at 24 mo underscore the importance of postnatal nutrition , which surely must be addressed. The evidence to date, however, suggests the impact of such interventions will be incremental without attention to the entire 1000 d. More research is needed to determine whether additive, or even synergistic, effects could be realized with a combination of early prenatal and postnatal interventions. With the strongest predictor of stunting (and length) at 24 mo being birth length, however, we surmise that substantial improvements in postnatal growth are likely to depend on improved intrauterine growth, especially during the critical first trimester.nqac051_Supplemental_FileClick here for additional data file.


Studies on the association between maternal dietary diversity and birth weight in offspring are limited, and the impact of such an adjustable factor on birth weight requires investigation to promote neonatal health. This study used data from a larger-scale population-based survey conducted in northwest China to evaluate the association of maternal dietary diversity with neonatal birth weight with a generalized estimating equation model. The results found that maternal dietary diversity was positively associated with neonate birth weight. Furthermore, a higher minimum dietary diversity for women (MDD-W) score during pregnancy was related to a lower risk of low birth weight (LBW) in offspring. The mothers with the highest MDD-W score had a 38%  lower risk of LBW than those with the lowest score. Similarly, the mothers with the highest animal-based food dietary diversity score (DDS) had 39%  lower risk of LBW in offspring compared with those with the lowest animal-based food DDS. Moreover, the ratio of animal-based food DDS to non-animal-based food DDS could play an important role in predicting neonate birth weight. In conclusion, increasing maternal dietary diversity would improve birth weight in offspring, especially by increasing the intake of animal-based foods among the Chinese population. Birth weight is an important evaluation indicator of fetal development in utero during pregnancy , and it The dietary intake of pregnant women should meet not only their own nutritional needs but also the needs of fetal growth ,10. The The dietary diversity score (DDS) is an evaluation index of dietary quality that assesses the diversity of all foods consumed in a given period, based on a simple count of food groups consumed . The FooData were from a population-based cross-sectional study conducted in Shaanxi of Northwest China. The detailed study design has been reported elsewhere ,26. BrieThe mothers were asked to recall food intake when they were pregnant with the young child. A semi-quantitative food frequency questionnaire (FFQ) was adopted to collect data regarding dietary food intake during the whole pregnancy. This FFQ was based on the previously validated FFQ designed for pregnant women in rural western China , and it MDD-W, as a dietary evaluation index for women with the minimum dietary diversity, is assessed based on main food categories . In the To prevent bias resulting from negligible consumption in a food group , the revAccording to the child’s birth certificate index in the survey, the gestational age, neonate birth weight, birth date, and gender were extracted. Birth weight was measured within 1 h of delivery using a baby scale to the nearest 10 g by the maternal and child health care staff in the local hospitals at or above the township. Gestational age was calculated from the last menstrual period or confirmed by ultrasound scan. Low birth weight was defined as neonatal birth weight < 2500 g .According to the previous studies ,34,35,36Family economic status, a comprehensive index, was established with principal component analysis (PCA) based on average monthly household expenditure, house condition, and vehicle ownership, which represented family economic level and was categorized as low, middle, or high based on tertiles . A comprn = 63), gestational weeks (n = 14), neonate gender (n = 97), average monthly household expenditure (n = 455), home ownership (n = 127), vehicle ownership (n = 127), maternal registered permanent residence (n = 38), initial antenatal examination (n = 145), antenatal examination (n = 24), genetic heredity counseling (n = 79), antenatal diagnosis (n = 72), folic acid supplements (n = 31), illness during pregnancy (n = 17), maternal education level (n = 17), and maternal career (n = 51), the method of multiple imputations was adopted to impute the missing values [Because there were some values missing for maternal age . Differences in the characteristics of women across three MDD-W groups were compared using ANOVA for continuous variables and Chi-square test for categorical variables. The proportion of mothers with an MDD-W score of one point and a mean MDD-W score for each food group was presented between LBW and non-LBW group.Considering that the participants were possibly clustered in counties of rural areas or districts of urban areas, the generalized estimating equation (GEE) models were used to explore the association between maternal dietary diversity and birth weight considering cluster effect. The GEE model is a population average model used to estimate the associations between health outcomes and neighborhood characteristics  in multilevel studies . In thisp values < 0.05.We also conducted subgroup analysis by main covariates to explore potential associations of interest across the subgroups. Furthermore, we completed a series of sensitivity analyses to examine the robustness of the association of interest. First, a quantile regression was used to investigate the impact of maternal dietary diversity across the whole distribution of birth weight. Second, considering the contribution of each food group to dietary diversity, the principal component analysis method was adopted to establish alternative dietary diversity score (DDS-PCA), which was used to explore whether the association of interest would change with different assessment methods for DDS. Third, the analysis was restricted to the participants with children aged less than 12 months in order to reduce the effect of recall bias. Last, the analysis was repeated in the participants with complete values of all original covariates. All analyses were performed using the SPSS 18.0 and R 4.2.1, and statistical significance was defined as p = 0.007) , mothers with the highest score (T3) tended to have a high family economic status, have a high maternal education level, be intellectual, have high antenatal examination level, live in urban areas, and take folic acid supplements during pregnancy. The neonate birth weight ascended with increases in MDD-W score (= 0.007) .p = 0.023). p < 0.05).The MDD-W score in LBW was significantly lower than that in non-LBW groups (5.82 ± 2.06 vs. 6.12 ± 1.97)   . To exam < 0.05) . When DD < 0.05) . When an < 0.05) . Similar < 0.05) .The present study provided a shred of additional evidence from the Chinese population that maternal dietary diversity was positively associated with neonate birth weight, even after adjustment for potential covariates. A higher MDD-W score was related to a lower risk of LBW. Compared with those in the lowest tertiles, the risk of LBW in offspring decreased by 38% among the mothers in the highest tertiles of overall MDD-W score. A more significant association could be found between animal-based food DDS and neonate birth weight. Besides MDD-W score, the ratio of animal-based food DDS to non-animal-based food DDS could be an important predictor for neonate birth weight. A series of sensitivity analyses further confirmed the association of interest.The main findings in the present study were similar to previous studies, but the effect size varied ,41. SaakSome studies have highlighted that low quality and high inflammatory potential maternal diet was associated with lower offspring birth size and a higher risk of offspring being born small-for-gestational-age . HoweverThe present study has several strengths. First, to our knowledge, it was the first study with a large sample to investigate the association between maternal dietary diversity and neonate birth weight among the Chinese population. Second, our study filled a gap in the research systematically analyzing MDD-W scores during pregnancy and their effect on neonatal birth weight. Third, in a manner distinct from existing studies in other countries, the MDD-W score in the present study was established based on the FAO’s recommendation and the Chinese Food Guide Pagoda. Thus, this index could be more appropriate for reflecting the dietary diversity of pregnant Chinese women. Fourth, previous data-driven dietary patterns have certain limitations in practical guidance, but MDD-W in the present study was more practical and operational. Distinct from previous studies, we limited the minimum food intake when including food groups to prevent overestimation of the results. Moreover, we further used principal component analysis to construct a new dietary diversity score (DDS-PCA) to improve the traditional MDD-W scoring method considering the influence of the biological contribution of diverse foods to diets. However, some limitations have to be addressed carefully when interpreting the results. First, the inference of causality is limited due to the nature of the cross-sectional design. Second, although we controlled for a series of covariates such as maternal age, folic acid supplements, and family economic status in the analysis, there were still some unobserved or unknown confounders that we could not fully investigate. For example, there was lack of maternal gestational weight gain which was related to reduced risks of LBW and SGA. Moreover, the survey was conducted from August to November. Taking into account the long pregnancy period of the participants, there was no special consideration for the influence of seasonal factors. Third, participants were from a regional survey in China, which partly limits the generalization of the results to the general Chinese population. Thus, results of the present study should be interpreted with caution. Fourth, the FFQ has a tendency of overestimating food intake , for whiBased on our findings, there are some practical implications of this study. Firstly, to health managers, the improvement of dietary diversity during pregnancy, especially by increasing the intake of eggs and dairy food, which is effective in the prevention and control of neonatal low birth weight should be taken into consideration. Maternal dietary nutrition management policies and measures should be amended by considering dietary diversity. Secondly, for maternal and child health workers, MDD-W is easy to understand and operate. In practice, the dietary quality of pregnant women can be generally understood by calculating the MDD-W score, so as to provide guidance for improving the diet during pregnancy. Thirdly, for pregnant mothers, the improvement of dietary nutrition during pregnancy should not only focus on the supplementation of specific food groups such as meat but also promote dietary diversity by intake of multiple food groups.In conclusion, increasing maternal dietary diversity, especially by increasing the intake of animal-based foods, would improve birth weight in offspring among the Chinese population. As a modifiable dietary factor, MDD-W could be used as a predictor in maternal dietary practice to improve maternal and children’s health. However, follow-up or intervention studies are needed to further determine this association and the mechanism behind it.


Despite simple and proven cost-effective measures were available to prevent birth asphyxia; studies suggested that there has been limited progress in preventing birth asphyxia even in healthy full-term neonates. In Sub-Saharan Africa, Inconsistency of magnitude of birth asphyxia and its association gestational age, Low birth Weight and Parity among different studies has been observed through time.This study aimed to estimate the Pooled magnitude of birth asphyxia and its association with gestational age, Low birth Weight and Parity among Neonates in Sub-Saharan Africa.2) test. Funnel plot and the Egger’s regression test were used to test publication bias. A weighted inverse variance random effects- model was used to estimate the pooled prevalence of birth asphyxia among neonates in Sub-Saharan Africa. STATA™ version 11softwarewasused to conduct the meta-analysis.PubMed, Cochrane library and Google scholar databases were searched for relevant literatures. In addition, reference lists of included studies were retrieved to obtain birth asphyxia related articles. Appropriate search term was established and used to retrieve studies from databases. Searching was limited to cohort, cross-sectional, and case-control studies conducted in Sub-Saharan africa and published in English language. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used for critical appraisal of studies. Heterogeneity across the included studies was evaluated by using the inconsistency index . low birth weight ), primigravida  andMeconium-stained amniotic fluid ) werevariables significantly associated with the pooled prevalence of birth asphyxia.The pooled magnitude of birth asphyxia was found to be high in Sub-Saharan Africa. Low birthweight and Meconium-stained amniotic fluid were variables significantly associated with birth asphyxia in Sub-Saharan Africa. Hence, it is better to develop early detection and management strategies for the affected neonates with low birth weight and born from mothers intrapartum meconium stained amniotic fluid. Birth asphyxia can be defined as the inability to initiate and sustainedbreathing at birth . AsphyxiIt is a situation that arises when there is impairment of blood gas exchange, which leads to hypoxemia, hypercapnia, metabolic acidosis, and multi organ failure . AccordiThe global incidence of birth asphyxia is estimated at 2 to 10 per 1000 among term newborns  and it iCauses of birth Asphyxia may be a maternal or fetal condition that happens before birth, during birth, or a combination of these –11. In dBirth asphyxia leads to various outcomes in the life of the neonate, such as multi-organ dysfunction,death, severe neurodevelopmentdelay, motor delay, cerebral delay, and hypoxic ischemic encephalopathy (HIE) –31.In Sub-Saharan Africathe burden of birth asphyxia is critical and public health problem that happened as a result of inadequate obstetrics health coverage, inaccessible health facilities, sociocultural norms, poor educational levels, shortage in health workers and supplies and poor health care spending. Likewise, facility deliveries, skilled delivery assistance and adequate antenatal visitswas lower in Sub-Saharan Africa regions , 32, 33.Despite simple and proven cost-effective measures were available to prevent birth asphyxia, studies suggested that there has been limited progress in preventing birth asphyxia even in healthy full-term neonates .As far as our search, the pooled prevalence of birth asphyxia was not previously investigated in sub-Saharan Africa. The findings of previous studies on the magnitude of birth asphyxia were inconsistent and ranged from 3.1%  to 39.7%The Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA) guideline  was usedIn order to obtain the significant articles international electronics databases such as PubMed, Google Scholar, and Cochrane library were retrieved. Two independent authors were assigned in order to systematically searching articles.In addition, other significant articles were retrieved manually from the gray literature by cross-referencing. The core search terms and phrases were “newborn”, “neonate”, “birth asphyxia”, “perinatal asphyxia”, “magnitude of birth asphyxia”, “and associated factors”, “Ethiopia”. The search strategies were developed using different Boolean operators. Particularly, to fit the advanced PubMed database, the following search strategy was applied: [ AND prevalence [MeSH Terms] OR incidence OR burden OR magnitude OR epidemiology AND (Associated factors) OR predictors OR determinant factors OR risk factors OR predisposing factors OR factors AND  that increase the occurrence of birth asphyxia were considered as exposure variables to estimate their effects on the magnitude of birth asphyxiaand the magnitude of birth asphyxia was considered as the outcome variable of this study.In order to remove duplicated studies, the retrieved articles were exported to reference manager software, Endnoteversion7. Two authors (MasreshaAsmareTechane (MAT) and SelamFisihaKassa (SFK)) screened and assessed the titles and abstracts of studies, followed by full-text assessments independently and systematically. Disagreements were resolved by consensus and discussion with other authors.Data were extracted by using the standardized Microsoft Excel data extraction form. Name of the first author, year of publication, country, region, study design, sample size, number of outcomes, prevalence (magnitude), risk estimate  with 95% confidence interval (CI) and associated factors were extracted from the included articles. The quality of the included studies was evaluated by using The Joanna Briggs Institute (JBI) quality appraisal checklist . Studies2 = 98.4%), Pooled analysis was conducted by using a weighted inverse variance random-effects model [The data were extracted from Microsoft Excel and analyzed using STATA Version 11. Meta-analysis was performed using statistical software. The funnel plot was used to check for publication bias, and Egger’s regression test was used to check for it more objectively . Heterogts model . A sensiMeconium-staned amniotic fluid: the presence of meconium in the amniotic fluid which changes the color of the liquor from clear to various shades of green, yellow or brownish color depending on the degree of meconium stained liquor .The search strategy retrieved 449 from Pub Med, 15 from Cochrane library and 12,500 from Google Scholar. 11,500 articles were removed due to duplicates, 657 due to unmatched title and abstracts, 456 due to study area. Three hundred fifty-one (351) articles were selected for the full text review. After full text reviews, 311 articlesdidn’t report the outcome of interest and excluded from the analysis. Finally, forty  articlesThirty-two studies were found in East Africa , 28, 41,The JBI quality appraisal criteria established for cross-sectional, cohort and case-control study design were used to appraise the included studies. The studies included in this systematic review and meta-analysis had no considerable risk. Therefore, all the studies were considered.2 = 98.4% ; IWe have done subgroup analysis by using region and study design of the included studies. Our subgroup analysis based on regions the study showed that the highest pooled prevalence of birth asphyxia was observed from studies done in East Africa  Fig. . But no p-value was 0.000, which indicated the presence of publication bias.Publication bias was evaluated by a funnel plot and the Egger’s regression test. A funnel plot showed asymmetrical distribution Fig.  subjectiWe have conducted a sensitivity analysis to assess the weight of every study on the pooled effect size of the magnitude of birth asphyxia. The sensitivity analysis using the Der Simonian-Laird random-effects model showed that there was no single study that affected the overall magnitude of birth asphyxia in Sub-Saharan Africa Fig. .fig. 5SeFrom the included forty studies, twelve , 28, 33 Out of the included forty studies, the association between low birth weight and birth asphyxia was reported in eight studies , 27, 44.From the included forty studies, the association between meconium stained amniotic fluid and birth asphyxia was reported in nine studies , 28, 44.Out of the included forty studies, the association between gestational age and birth asphyxia was reported in ten studies , 18, 27.In developing countries, birth asphyxia remains the main cause of neonatal morbidity and mortality , 45, 46.In our study, the pooled prevalence of birth asphyxia in Sub-Saharan Africa was found tobe17.28% . This finding is consistent with findings from other systematic review and meta-analysis done in Central and West Africa 15.9% . This vaThe magnitude of birth asphyxia varied greatly in the included studies, ranging from 3.1%  to 39.7%This finding reveals the presence of a strong association between birth asphyxia and low birth weight. The odds of a newborn developing birth asphyxia was 2.58 times higher among newborns with low birth weight than among newborns with normal birth weight. This finding is in line with various studies conducted in Indonesia , PakistaThis systematic review and meta-analysis alsoshowed that the presence of meconium-stained amniotic fluid increases the occurrence of birth asphyxia. This finding is consistent with studies conducted in India , PakistaThis study had its limitations. Primarily, most of the studies included for this analysis had a small sample size, which could have a significant effect on the estimated pooled prevalence of birth asphyxia. Furthermore, majority of studies included in this systematic review and meta-analysis were conducted in East Africa, which may be an underrepresentation for the other region of sub-Saharan Africa. Since it is a first systematic review, lack of enough literature and use odds ratio to estimate the predictor variables may be affected by other confounding variables. Moreover, only articles and reports published in English were considered in this review, which sought to investigate birth asphyxia in the Sub-Saharan Africa. In addition, the majority of studies included in the review were cross-sectional in nature, which limited our ability to assess cause–effect relationships and might have resulted in the outcome variable being affected by other confounding variables.Findings from this study indicated that birth asphyxia in Sub-Saharan was Still the major public health problem. This study also noted that birth asphyxia was significantly associated with low birth weight and meconium-stained amniotic fluid. Hence, it is better to assess all neonates with birth asphyxia for low birth weight and intrapartum meconium-stained amniotic fluid. Moreover, further research is needed to identify other predictors of birth asphyxia in Sub-Saharan Africa.