The correlates of prenatal and postnatal growth on Intelligence Quotient (IQ) in childhood in term-born children living in high-income countries are not well known.We examined how birth size and growth in infancy and childhood were associated with IQ at age 5 y in term-born children using path analysis.z-scores.The study sample comprised 1719 children from the Danish National Birth Cohort who participated in a substudy in which psychologists assessed IQ using the Wechsler Primary and Preschool Scales of Intelligence–Revised. Measured weight, length/height, and head circumference at birth, 5 mo, 12 mo, and 5 y were included in a path model to estimate their total, indirect, and direct effects on IQ. All growth measures were included in the model as sex- and age-standardized z-score increase from 5 to 12 mo, IQ increased by 1.53  points] whereas weight gain from 12 mo to 5 y was not associated with IQ. Height and head circumference growth in childhood was associated with IQ .After adjusting for potential confounders, a positive association between birth weight and IQ was observed, and 88% of the association was direct. Weight gain in infancy was associated with IQ [per In children born at term in an affluent country with free access to health care, higher IQ was seen with greater size at birth and greater weight gain in infancy. Also, greater growth in height and head circumference throughout the first 5 y of life was associated with higher childhood IQ whereas greater weight gain after the first year of life was not. Nutrition is needed for growth including development of the brain , and stuThis study was based on data from the Lifestyle During Pregnancy Study (LDPS) nested within the Danish National Birth Cohort (DNBC), which has been described in detail elsewhere , 24. BriThe DNBC was approved by the Scientific Ethics Committee in Denmark and the Danish Data Protection Agency, and the latter also approved the present substudy. All the participants in the DNBC provided written informed consent.z-scores for weight, length, and head circumference  covering all births in Denmark. All these measures were carried out by midwives before leaving the delivery room. At the second postpartum interview, ∼18 mo after birth, the mothers reported the child's weight, length, and head circumference measured at routine check-ups by their GP when the child turned 5 mo and 12 mo old as well as the exact dates of the measurements. The GPs followed national standards for measuring weight and length. Length was measured in a supine position to the nearest half centimeter, and weight was measured with 1 decimal place on a validated scale. The GP reported this information in the child's personal book, a health record kept by the parents and used to communicate between them, health professionals visiting the family at home, and the GP. At the 5-y LDPS follow-up, the research staff measured growth parameters of the child  once, with the children wearing no shoes and light clothes. To increase comparability with other populations, we used the UK-WHO growth reference to calculate standardized sex- and age-specific mference . To limiCognitive function as estimated by IQ was assessed as part of a 3-h neuropsychological assessment conducted by 10 trained psychologists following standardized test procedures  using thSupplemental Figure 1. From the MBR, we obtained information on gender, maternal age at conception, birth order, and gestational age at birth. Information on socio-occupational status, maternal prepregnancy BMI as well as leisure-time exercise came from the first pregnancy interview. Socio-occupational status was categorized as high , middle , or low (unskilled work or unemployment) (2) was estimated based on self-reported weight and height, and exercise in pregnancy was categorized as no exercise, 1–180 min/wk, or >180 min/wk. The FFQ information was used to characterize Western, intermediate, or health-conscious dietary patterns during pregnancy  . Prepregregnancy . Smokingregnancy  and Raveregnancy . Raw scon = 8) were kept in the study population to examine the whole birth size distribution in children born at term.Of the 1782 children who participated in the neuropsychological assessments, the full IQ score was available for 1771 of the children; 97% of these were born at term, thus the study population encompassed 1719 children . Childrez-scores of weight, length/height, and head circumference) and IQ, we used path analysis, a subset of structural equation modeling. Path analysis is an extension of regression analysis that simultaneously estimates the linear associations between all path variables and makes it possible to assess the total, direct, and indirect effects of each path variable .Although some participants had missing information on some variables, they were all included in the analyses and contributed with all available information by using the estimation by maximum likelihood with missing values method . This moSupplemental Table 1.All statistical analyses were weighted by sampling fractions because higher alcohol categories were oversampled in the LDPS. Furthermore, in model A, we adjusted for the following covariates at relevant regressions in our path analysis see : sex, biFinally, we generated restricted cubic splines  to describe any significant associations between growth and childhood IQ in more detail by allowing a nonlinear association. In contrast to the path analyses, these analyses do not cope with missing data and multiple imputation was therefore used. Fifty copies of the dataset were generated, each of which had its missing values imputed by chained equations , 40. VarAll statistical analyses were performed by using Stata/SE 15 (StataCorp).n = 1719). The average maternal age at conception was 30 y, most of the mothers had above average socio-occupational status, and few of the mothers and fathers were obese before pregnancy. Of the children, 52% were boys and 52% were firstborns. Average birth weight was 3630 ± 486 g, length was 52.5 ± 2.2 cm, and head circumference was 35.4 ± 1.6 cm. Seventy-five percent of participants were breastfed fully or partially for >20 wk, and 75% of participants were introduced to solid food at the age of 4–5 mo.z-scores on IQ at the age of 5 y are presented in The average IQ score for boys was 103.8 ± 13.4, and for girls 107.7 ± 11.8. Total, indirect, and direct effects of weight-for-age, height-for-age, and head-circumference-for-age z-score increase, the IQ score increased by 1.22  points. Also, length and head circumference at birth were positively but nonsignificantly associated with IQ in childhood. The effects of all 3 growth measures on IQ were mainly direct (68–88% of the effect was direct), suggesting an association of birth size not mediated through later growth.We observed that greater weight at birth was associated with higher IQ in childhood; per Increasing weight gain in early infancy was indirectly associated with higher IQ, thus mediated through greater weight at 12 mo. Also, weight gain in late infancy was positively associated with IQ; however, this association was direct. This means that it was not mediated through a subsequent greater weight at 5 y. In contrast, gain in length and head circumference in late infancy were mainly observed to be indirectly associated with IQ, meaning that the positive effects were mediated through a greater height and head circumference at 5 y.z-score increase in height and head circumference at 5 y, the IQ was 0.98  and 2.09  points higher, respectively. This supported the previously mentioned indirect effect of length and head circumference in late infancy mediated through greater height and head circumference in childhood. In contrast, greater weight gain in childhood from 12 mo to 5 y seemed not to be associated with higher IQ in childhood. Instead, the estimate indicated a weak negative association with IQ [−0.12 ].For growth in childhood, we observed that increased growth in height and growth in head circumference were associated with a higher IQ. Thus, per z-scores. Similarly, the positive association between greater height and head circumference at 5 y and IQ, adjusted for previous growth measurements, also leveled off around 1 to 1.5 z-scores.Restricted cubic splines (In children born at term in a high-income country, we observed that both prenatal and postnatal growth were associated with positive increments in childhood IQ. Greater size at birth, especially birth weight, was positively related to IQ, independent of later growth. Also, growth in infancy, especially weight gain and growth in head circumference from 5 to 12 mo of age, were positively associated with IQ. In the childhood period, after adjusting for previous growth, we found both greater gain in height and in head circumference between 12 mo and 5 y to be positively related to IQ, whereas greater weight gain in the same period seemed not to be associated with IQ.Others have observed a positive association between birth weight and childhood IQ , 18, andThe children in our study population were all living in a high-income country with taxpayer-funded access to health care, and most of them had mothers with above average socio-occupational status. Thus, it is likely that they did not suffer from undernutrition or severe and prolonged infectious diseases affecting growth . HoweverStrengths of our study include the longitudinal design and the ability to include the 3 growth measures, weight, length/height, and head circumference, at all time points. This allowed us to examine if change in growth from birth throughout the first 5 y of life was related to childhood IQ. Also, by separating the different growth measures, we were able to study their independent contribution. We applied a statistical approach that provided insight into potential direct and indirect pathways between prenatal and postnatal growth and childhood IQ. Moreover, the present study is a substudy within the DNBC, which contains extensive information on several potential confounders including breastfeeding  and mateOur study also has some limitations that should be addressed. Although growth parameters were measured by health professionals, measurement errors are inevitable, perhaps more for length and head circumference than for weight, and perhaps more for length at birth/infancy than height in childhood. We would expect such measurement errors to be unrelated to the outcome, potentially attenuating the associations. Further, childhood growth was defined as growth from 12 mo to 5 y, which is a long period that could hide important variation, and ≥1 measurements in that period would have provided more detailed information on influence of growth in specific periods of childhood. Despite the fact that women of higher socioeconomic status were overrepresented in the DNBC , and ourIn conclusion, we observed that in children born at term with free access to health care, growth in utero and up until the age of 5 y was positively associated with childhood IQ. Greater birth size in itself was an indicator of higher IQ, with weight gain as the strongest growth parameter until 12 mo of age. After 12 mo until 5 y of age, growth in height and head circumference were most important. The effect sizes we observed could be important on a population level, and even small changes in a nation's IQ have been shown to influence human capital and economic living standards . Thus, wnqaa051_Supplement_FileClick here for additional data file.


Polycyclic aromatic hydrocarbons (PAHs) are a kind of endocrine disruptors, which can enter human body by the inhalation of PAH-containing matter and the ingestion of PAH-containing foodstuffs. Studies showed that PAHs can cross the placental barrier and might cause adverse effects on the fetus.This meta-analysis aimed to estimate the associations between prenatal exposure to PAHs and birth weight.Articles published in English until May 8, 2020 and reported the effects of prenatal exposure to PAHs on birth weight were searched in multiple electronic databases including PubMed, the Web of Science, EMBASE and the Cochrane Library. The included studies were divided into three groups in accordance with the measurement of PAHs exposure. Then coefficient was extracted, conversed and synthesized by random-effects meta-analysis. And risk of bias was assessed for each study.A total of 3488 citations were searched and only 11 studies were included finally after double assessment. We found that there were no association between PAH-DNA adducts in cord blood (low/high) , 1-hydroxy pyrene (1-HP) concentration in maternal urine  and prenatal maternal airborne PAHs exposure  and birth weight. However, we observed ethnicity may change the effects of PAHs exposure on birth weight.There is no significant relationship between prenatal exposure to PAHs and birth weight in our meta-analysis. Further studies are still needed for determining the effects of prenatal PAHs exposure on birth weight. Growing number of studies showed that air pollution might play an important role in the occurrence of adverse pregnancy outcomes –3. A numThe fetal period is a critical period in the development of various systems, during which even slight exposure to chemicals might adversely affect morphology and functions of the systems. Birth weight is an important indicator of fetal growth and nutritional status, which is closely associated with a series of adult health outcomes. Previous studies have suggested that lower birth weight was associated with infant mortality, cardiovascular disease, stroke and type 2 diabetes –8. AdditPAHs are generally produced during incomplete combustion processes. Over the past few centuries, as the abundant use of fossil fuels for industrial applications, heating, transport, the emissions of PAHs have become more and more serious. Thus, PAHs are ubiquitous pollutants in both the general environment and in certain working environment , 15. As A number of recent studies have estimated the association between PAHs exposure during pregnancy and birth weight, but the conclusions were inconsistent and controversial –20. AlthTherefore, we performed a meta-analysis to assess the effects of prenatal exposure to PAHs on birth weight. Since humans can be exposed to PAHs through the respiratory tract by inhalation of PAH-containing matter  and the digestive tract by intake of PAH-containing foodstuffs  . The expwww.crd.york.ac.uk/PROSPERO) under protocol number CRD42019147060 and developed in accordance with the PRISMA Guidelines in the preparation of this manuscript (www.prisma-statement.org).Our review was registered with PROSPERO (3) incremental increase in airborne PAHs, high versus low PAH-DNA adducts in the umbilical cord blood and per ln unit μg/g creatinine (about 2.72 μg/g Cr) incremental increase in concentration of 1-HP in maternal urine; and Outcome–birth weight. Based on this, the following research question was established: for newborns, what are the incremental effects of per ln unit exposure to airborne PAHs, high level of PAH-DNA adducts in the umbilical cord blood and per ln unit increase of 1-HP in maternal urine during gestation on birth weight.The research question was determined using the PECO strategy: Population–newborn and their mother; Exposure–airborne PAHs, PAH-DNA adducts in the umbilical cord blood and 1-HP in maternal urine; Comparison–per Natural logarithm (ln) unit  were written in English; 2) just included singleton live birth; 3) were cohort, cross-sectional studies or case control study included only human subject; 4) studied maternal exposure to PAHs during pregnancy and in trimester-specific periods; 5) had excluded women with pregnancy complications or adjusted pregnancy complications as confounding factors; 6) presented the sample sizes and linear regression coefficient (β) with 95% confidence intervals (CIs). In addition, some studies with following criteria were excluded: 1) included premature birth (< 37 weeks) and post-term birth (> 42 weeks) but the gestational week was not adjusted. Studies met all of the above selection criteria were listed for inclusion in the review. When more than one study was determined for a given population, only one study including either the most recent population data or the last information, or both, was selected. Urinary 1-HP is associated with genotoxicity and can serve as a biomarker for internal exposure to PAHs, and the PAH-DNA adducts are also suitable biomarkers for effective dose of PAHs . PreviouWe searched on PUBMED, the Cochrane Central Register of Controlled Trials (the Cochrane Library), the Web of Science and EMBASE.We limited our search to papers published in English until May 8, 2020. All related terms were used for retrieval, such as “polycyclic aromatic hydrocarbons”, “PAH*, “birth weight”, “maternal exposure”, “pregnan*”, “gestation”, “conception”, “gravid*”, “maternal-fetal relations”, “pregnancy outcome”, “birth outcomes”, “birth weight”, “infant”, “newborn”. Full details were provided in the supplementary information . In addiTwo authors worked independently and verified the abstracts and titles of the search results. The differences were resolved by discussion or consultation with a third party to reach consensus. All potentially relevant articles were screened for full text. Where there were differences of opinion, the third author who did not evaluate the articles initially would review it to arrive at a final decision among the three authors. Any reasons for rejection were clearly recorded for the studies that met the inclusion criteria.Two authors extracted data using standard template of data extraction independently. The regression coefficients, standard errors, t-values, p-values, mean and median birth weight and 95% confidence intervals of PAHs and birth weight were collected.A Microsoft Excel spreadsheet was used to extract information from eligible studies. The following information was extracted: author, year, title, study design, location and ethnicity, study period, sample population, mean or median age and measure of dispersion, exposure measures, birth weight measures, significance of association, confounders, etc.The risk of bias for each included study was accessed using a novel risk of bias instructions for assessing exposure to air pollution developed by Lam . Since t3, and the unit of the concentration of PAH-DNA adducts in cord blood is adducts/108 nucleotides, while the unit of the concentration of 1-HP in maternal urine is μg/g Cr. Heterogeneity was quantified by I2 statistics. When significant heterogeneity was present (I2> 0.5), a D-L random-effects model meta-analysis was performed to merge effect value. Otherwise, a fixed-effect model meta-analysis was performed. Meta-analysis was performed using “metafor” package in R version 3.6.1. Significance level was set at P < 0.05.Prior to conducting the meta-analysis, coefficients and their confidence intervals for the associations between PAHs exposure and birth weight from included studies were extracted. Under normal distribution assumption, standard errors (SEs) of the coefficients were calculated by coefficients and their CIs, P-value, sample size and the number of regression parameters with R version 3.6.1. When articles did not report exact P-value, the upper limit of the P value was conservatively taken as the estimated P value on the premise of not changing the total effect  . In addiA total of 3488 citations  were assessed with the inclusion and exclusion criteria, and after excluding repetition, there were 3,488 remaining. A flowchart of the study selection process was depicted in The results showed that these studies had moderate quality. The risk of bias ratings for included studies showed a “PROBABLY HIGH risk of bias” about potential confounding in PAH-DNA adducts of cord blood and 1-HP concentration of maternal urine , 36, 38.3 increase of airborne PAHs was not significantly associated with birth weight , with a high heterogeneity (I2 = 87.17%)  . And eth 87.17%) 2 = 57.13%) ( 57.13%) . A study 57.13%) 2 = 0.00%) studies was very low. Two studies gave only brief descriptions of the participants, so they were considered as “PROBABLY HIGH” risk of bias. Potential confounding of two studies were considered as “PROBABLY HIGH” risk of bias for lack of important covariates (ETS). (s (ETS). In this meta-analysis, we provided a summary of the current scientific evidence, and evaluated the overall association between prenatal exposure to PAHs and birth weight. We found that there were no associations between prenatal maternal exposures to airborne PAHs, PAH-DNA adducts in cord blood (low/high) and 1-HP concentration in maternal urine and birth weight. We identified 11 previous researches that link PAHs to birth weight. The regression coefficient of birth weight ranged from -0.21 to 0.117 across the studies. As a whole, most studies were rated as “Low” or “Probably Low” risk of bias in most domains, but one third of the studies had a “Probably High” risk of bias in potential confounding.3 increase) during gestation on term birth weight revealed a non-significant positive role . This pooled result was consistent with one included study conducted in the NYC Dominican, but the other three included studies all had suggested significantly effects of maternal exposure to airborne PAHs on birth weight , 2422, 2Subtle genetic differences among different races leads to different levels of DNA adducts under ‘PAH low’ and ‘PAH high’ conditions, which may be related to the effect of gene mutation on DNA damage and repair. Iyer et al. , 46 had CYP1A2 and CYP1B1, which are related to PAHs metabolism, detoxification and repair. And at higher exposure levels, there may be higher baseline levels of these enzymes for PAHs induction [In addition, the effect difference between Polish Caucasians and NYC African Americans and Dominicans can be explained by the threshold effect to a certain extent. Polish Caucasians had more than 10-fold higher PAHs exposure risk than NYC African Americans and Dominicans, which is consistent with the higher levels of air pollution in Poland . And a snduction . Only whSeveral limitations should be addressed. Our review covered limited studies in each group, so the test efficiency of publication bias might be insufficient, and the power of the tests for funnel plot asymmetry might be too low to distinguish chance from real asymmetry . There wFurther large cohort studies with sufficient data and reliable exposure data are still required to get a better understanding of the associations between PAHs and birth weight. Meanwhile, subsequent studies should consider more comprehensive confounding factors, including more regional populations and more ethnic participants. Subgroup analysis by race is also necessary, which may help to identify high-risk groups.This meta-analysis showed that there was no relationship between maternal PAHs exposure and the risk of term birth weight. Additionally, we have identified potential sources of the heterogeneity, including ethnicity, regions, and exposure levels. We also observed that ethnicity may change the effects of PAHs exposure on birth weight, but the studies were too small to conduct a subgroup analysis. Therefore, future reliable large cohort studies are required for a better understanding of the associations, which might help to identify high-risk groups.S1 Checklist(DOC)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.


Previous studies suggested that singletons from frozen-thawed embryo transfer (FET) were associated with higher risk of large, post-date babies and adverse obstetrical outcomes compared to fresh transfer and natural pregnancy. No data available revealed whether the adverse perinatal outcomes were associated with aberrantly high progesterone level from different endometrium preparations in HRT-FET cycle. This study aimed to compare the impact of progesterone intramuscularly and vaginally regimens on neonatal outcomes in HRT-FET cycles.A total of 856 HRT-FET cycles from a fertility center from 2015 to 2018 were retrospectively analyzed. All patients had their first FET with two cleavage-staged embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone intramuscularly 60 mg per day or vaginal gel Crinone 90 mg per day. Pregnancy outcomes including live birth rate, singleton birthweight, large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm delivery rate were analyzed. Student’s t test, Mann-Whitney U-test, Chi square analysis, and multivariable logistic regression were used where appropriate. Differences were considered significant if p < 0.05.No significant difference of live birth rate was found between different progesterone regimens . Neonatal outcomes like singleton birthweight (p = 0.744), preterm delivery rate , SGA , and LGA rate  were not different between two progesterone regimens. Serum P level >41.82 pmol/L at 14 day post-FET was associated with higher live birth rate than serum P level ≤41.82 pmol/L in HRT-FET cycles when progesterone was intramuscularly delivered . But singleton birthweight, preterm delivery rate, SGA and LGA rate were not different between these two groups.Relatively higher serum progesterone level induced by intramuscular regimen did not change live birth rate or neonatal outcomes compared to vaginal regimen. Monitoring serum progesterone level and optimizing progesterone dose of intramuscular progesterone as needed in HRT-FET cycles has a role in improving live birth rate without impact on neonatal outcomes. As cryopreservation has been an efficient and reliable laboratory procedure, freeze-all policy and elective embryo cryopreservation have been increasingly prevalent with a variety of clinic indications like preventing OHSS, implantation of PGT-A, fertility preservation, etc . There iProgestin directly advanced vascular proliferation during placentation . A supravia IVF and FET were excluded from the study. The final database included 856 women and 240 live birth singletons in the criteria. We kept patients re-examined in the first trimester and followed up by phone calls after the first trimester.The retrospective study was undertaken at the assisted reproduction medicine department in Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine, including 856 women who had undergone their first FET from January 2015 to December 2018. Inclusion criteria were maternal age <48, undergoing two Day 2 or Day 3 cleavage-stage embryos transfer following HRT endometrium preparation. The patients with cryopreserved oocytes or donor oocytes and with prior attempts at conception 2 and 6% CO2 concentration. Embryo development was evaluated on Days 2, 3, 5 and 6. Day 2 or Day 3 cleavage-stage embryos with at least two or six blastomeres respectively and with fragmentation <20% according to guidelines  6 mg per day with or without adding estrogen vaginally (Estradiol Femoston) 2 mg per day. Transvaginal ultrasonography, serum E2, LH, and progesterone level were measured at each visit weekly. Once the time of FET was determined, progesterone intramuscularly (60 mg per day) or vaginal gel Crinone (90 mg per day) was initiated daily. They both combined with dydrogesterone orally 30 mg per day and estradiol orally 6 mg per day. Intramuscular Progesterone or Vaginal Crinone was chosen according to patient preference after fully informing them with the advantages and side-effects of different routes such as vaginal itch and discharge or the subcutaneous swell experienced with intramuscular injection. Patients who were undertaken Day 2 or Day 3 cleavage-staged embryo transferred started the progesterone 2 or 3 days before FET, respectively. The vitrification and thawing procedure were previously presented . Embryo In order to evaluate the impact of progesterone delivered regimens on clinical outcome, the primary outcome measure was live birth rate. Secondary outcome measures included clinical pregnancy rate, newborn birthweight, large for gestational age (LGA), small for gestational age (SGA), preterm delivery rate. Live birth was defined as a delivery of a viable infant after the 28th gestational weeks. Clinical pregnancy is a pregnancy confirmed by the confirmation of gestational sac or heartbeat. Gestational age was calculated from 14 days before the embryo transfer. Preterm birth was defined as delivery between 28 to 37 gestational weeks. SGA and LGA were defined as birthweight <10th and >90th percentile, respectively. Z score was administered to calculate birthweight adjusted for gestational age and newborn gender using the formula: Z score = (χ−μ) / σ, where χ is the birthweight of the infant, μ is the mean birthweight for the same sex and same gestational age in the reference group and σ is the standard deviation of the reference group. The reference is the Chinese singletons newborns .Patients and singletons live birth demographic baseline, cycle characteristics, clinical and neonatal outcomes were compared using Student’s t-test, Mann-Whitney U test, chi-square, and Fisher’s exact tests, as appropriate. Whether binary live birth and clinical pregnancy were modified by the regimens of progesterone was assessed by multivariable logistic regression adjusting for major covariates as maternal age, BMI, the route of estrogen administered, whether duration of estradiol treatment >21 days, whether at least one good quality embryo was transferred. Multivariable logistic regression was applied to evaluate the regimens of progesterone impact on neonatal outcomes adjusting for the major covariates mentioned above plus newborn gender. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were reported. All analyses were conducted with SPSS statistics. P value < 0.05 was considered statistically significant.Institutional review board and ethics committee of Shanghai General Hospital approval was obtained.versus 14.95 pmol/L). No significant difference of live birth rate  and clinical pregnancy rate  was found between different progesterone regimens . Money was to appreciate the hard work of all authors.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.


Most studies have mainly focused on the effects of the sperm DNA fragmentation index (DFI) on fertilization, embryonic developmental potential and aneuploidy, pregnancy and abortion rates after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and have remained controversial. However, few studies have reported the effects of sperm DFI on neonatal outcomes, including stillbirths, neonatal deaths, sex, gestational age, prematurity, birthweight, low birth weight (LBW) and birth defects in newborns. Our objective was to evaluate the effects of sperm DFI on the clinical and neonatal outcomes of ICSI cycles.This retrospective study analysed a total of 2067 oocyte retrieval, 1139 transfer and 713 delivery cycles from conventional ICSI cycles, including 301, 469, and 214 live-born infants in groups segregated according to sperm DFI as the < 15%, 15–30% and >  30% groups, respectively. The clinical and neonatal outcomes were compared among the three groups.Sperm DFI did not significantly affect the rates of fertilization, clinical pregnancy, miscarriage or ongoing pregnancy. Sperm DFI did not increase the risk of stillbirths or neonatal deaths. The rates of stillbirths and neonatal deaths were not significantly different among the three groups. The sex, gestational age, prematurity, birthweight and LBW of newborns in the three groups were not significantly affected by sperm DFI. Moreover, sperm DFI did not increase the number of birth defects in children.Sperm DFI did not affect the clinical or neonatal outcomes of ICSI cycles. The integrity of sperm DNA is important for embryonic development and pregnancy. Sperm DNA damage is even frequently found in normozoospermic men . Sakkas Santi et al.  reportedAt present, most studies have mainly focused on the effect of sperm DFI on fertilization, embryonic developmental potential and aneuploidy, pregnancy and abortion rates. However, few studies have reported the effect of sperm DFI on neonatal outcomes, including stillbirths, neonatal deaths, sex, gestational age, prematurity, birthweight, low birth weight (LBW) and birth defects in newborns. In addition to the clinical outcomes, our retrospective study compared the effects of different sperm DFIs on neonatal outcomes in ICSI cycles.All patients signed informed consent forms for ICSI and follow-up from August 2015 to December 2017 before participating in this retrospective study. All male patients were submitted to the same methods to measure sperm DFI in a sperm chromatin structure assay (SCSA) performed 1–2 months prior to oocyte retrieval. DFI values were used to categorize the subjects into three groups: < 15%, 15–30% and >  30%. Cycles performed in patients with normal chromosomes, who did not receive antioxidant therapy prior to their IVF procedures and underwent day 3 embryo transfer were included in this study. Cycles from day 2 embryo and day 5 blastocyst transfer were excluded from this study. A total of 2067 oocyte retrieval, 1139 transfer and 713 delivery cycles, including 301, 469, and 214 live-born infants from < 15%, 15–30% and >  30% groups, respectively, were studied in this retrospective study.The published literature  was usedData on the clinical outcomes and neonatal outcomes, including clinical pregnancy, miscarriage, the date of birth, sex, live-birth or not, birthweight and birth defects in newborns, were gathered through phone calls and electronic database registration.2 test was used to compare rates among the three groups. P <  0.05 indicated statistical significance.SPSS 22.0 software was used for all data analyses. An independent samples Kruskal-Wallis test was used to compare means among the three groups. The χDuration of infertility and male BMI were not significantly different among the three groups. Female BMI in high sperm DFI group 15–30%) was significantly lower compared with that in low sperm DFI group (< 15%), while the distribution of primary infertility and thickness of the endometrium in the 15–30% group were significantly higher compared with that in the DFI <  15% group. Female age and male age were significantly different among the three groups, while sperm DFI significantly increased as female age and male age increased  in the DFI <  15% group, and there were four birth defects , cleft soft palate (1), congenital heart disease (1), and joint deformity of the left index and middle fingers (1)) in the 15–30% group and two birth defects (Down syndrome (1) and an extra finger near the right thumb (1)) in the DFI >  30% group. There were no significant differences in birth defects among the three groups  and low (< 30%) sperm DFI groups from IVF or ICSI cycles . A prospSimon et al. reported that infertile couples with high sperm DFI had a much lower live-birth rate after conventional IVF than infertile couples with a low sperm DFI, while there was no significant difference in live-birth rate in couples undergoing ICSI cycles . A systeIt has been reported that the incidences of prematurity and LBW in newborns are significantly higher after IVF/ICSI than for natural conception , 25. SegSperm DNA damage is often accompanied by numerical and structural chromosomal abnormalities of spermatozoa , 29, whiIn the present retrospective study, ejaculated spermatozoa were utilized for conventional ICSI. To obtain better clinical outcomes, Bradley et al.  reportedSperm DFI did not compromise the clinical and neonatal outcomes of newborns in our retrospective study. Multicentre and randomized controlled trials are needed to confirm our conclusion.


ST standards, at preschool age with World Health Organization (WHO) child growth standards. The employment of INTERGROWTH-21ST Preterm Postnatal longitudinal standards during the in-hospital follow-up significantly reduced the diagnosis of short term extrauterine growth restriction when compared to commonly used cross sectional neonatal charts, with significant lower loss of percentiles between birth and term corrected age (p < 0.0001). The implementation of a package of standards at birth, preterm postnatal growth standards and WHO child growth standards proved to be consistent, with correlation between centile at birth and at follow-up, and therefore effective in monitoring growth in a moderate and late preterm infant cohort without chronic or major morbidities. Infants identified as small for gestational age at birth showed significantly more frequently a need for auxological referral.Preterm infant growth is a major health indicator and needs to be monitored with an appropriate growth curve to achieve the best developmental and growth potential while avoiding excessive caloric intake that is linked to metabolic syndrome and hypertension later in life. New international standards for size at birth and postnatal growth for preterm infants are available and need implementation in clinical practice. A prospective, single center observational study was conducted to evaluate the in-hospital and long-term growth of 80 preterm infants with a mean gestational age of 33.3 ± 2.2 weeks, 57% males. Size at birth and at discharge were assessed using the INTERGROWTH-21 Monitoring preterm infant growth is a key point in the assessment of these children during hospitalization and after discharge from neonatal intensive care unit. ,2Weight gain evaluation is used in clinical practice as a guidance to individualize nutritional intakes: as a consequence, the choice of an appropriate reference growth curve is key to achieve the best developmental and growth potential while avoiding excessive caloric intake, that is linked to metabolic syndrome and hypertension later in life. ,4In the past, fetal growth was considered the standard of growth also for the preterm neonate;  nowadaysST Project [International standards for size at birth and postnatal growth standards for preterm infants have been developed within the INTERGROWTH-21 Project , using t Project ,8 TestinFinally, since we are dealing with relatively new size at birth standards ,10, therST centiles at birth [To summarize, the present observational study was conducted in order to (1) evaluate the in-hospital growth of a population of preterm infants and the prevalence of growth failure at discharge using preterm standards compared to widely used size-at-birth charts ,12; (2) at birth ,10 of that birth ,14; (3) All infants admitted after birth to the Special Care Unit for Infants of Regina Margherita Children Hospital, Turin, Italy who have reached an age of 4 to 5 years between 1st December 2018 and 31st December 2019 (3 months deviation from the indicated ages was tolerated) were assessed for inclusion in this prospective, single center observational study.Gestational age at birth ≥ 37+0 weeks;Syndromes, conditions or diseases known to affect growth and/or requiring specific charts, e.g., Down’s syndrome or other genetic syndromes, short bowel syndrome, etc.;Chronic diseases which required prolonged parenteral nutrition.Exclusion criteria were:A total of 237 children were assessed for eligibility. A total of 124 subjects were preterm and met inclusion criteria and parents were called by phone in order to invite them to take part into the study: of those, 33 had invalid phone number, 11 refused to participate. Finally, 80 infants born preterm were included in the study.Obstetric antenatal charts were reviewed in order to record gestation complications and IUGR, defined according to the recommendations of the American College of Obstetricians and Gynecologists Neonatal records were also examined to get exact data about length of hospital stay, feeding practices during hospitalization and early morbidities.Weight, length or height and head circumference were taken at birth as well as at term corrected age and at the follow-up visit by a trained anthropometrist using an electronic scale, Harpenden stadiometer and SECA craniometer (non-extensible tape). Parents’ heights were measured in order to calculate child’s statural target ,14.At the follow-up visit all participants underwent a physical examination. Parents completed a questionnaire enquiring data on the child’s health, feeding practices, acquired vaccinations and reaching the developmental milestones.Anthropometry at birth was plotted on INTERGROWTH-21st size at birth standards ,10, anthChildren with unsatisfactory growth were referred to auxological follow-up with the following criteria: statural height lower than third percentile on WHO standards and/or height-growth-percentile falling outside parent targets and/or reduced growth velocity for sex and age calculated longitudinally with at least two measurements during follow-up. ,14 ParenSmall for gestational age (SGA) was defined as with birth weight below the 10th percentile ,18.Parents or guardians gave informed consent for inclusion of their children before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki and the protocol was approved by the Ethics Committee of Torino, code 219/2010.t-test, chi-squared test or analysis of variance (ANOVA), for example to assess the correlation between measures at birth and at follow-up. Statistical analysis was conducted using IBM® SPSS® Statistics 24.0 software.Depending on the variable and on its distribution, Eighty children  were recruited. Average age at the time of clinical evaluation was 4.21 ± 0.28 years. Additional baseline characteristics are reported in p < 0.0001).In order to assess the so-called extrauterine growth restriction, the variation of weight percentiles between birth and term “corrected” age was calculated, comparing results obtained using INTERGROWTH-21st ,10,11 anp = 0.436 for weight, p = 0.638 for length/height and p = 0.975 for head circumference, using t-test)  were evaluated, resulting normally distributed. Percentiles at birth (according to INTERGROWTH-21st) ,10 and a t-test) a–c.p-value of 0.004 for length/height and of 0.046 for head circumference.Significant individual positive correlations between percentiles of length and head circumference at birth and of height and head circumference at follow-up were detected, respectively with a moderate and a weak correlation An increase of one percentile of length at birth determined an increase of 0.352 percentiles of height at follow-up, while an increase of one percentile of head circumference at birth determined an increase of 0.214 percentiles of head circumference at follow-up.2 = 4.595; p = 0.032), while subjects who were identified as IUGR during intrauterine life (being or not SGA at birth) did not (p = 0.676).Children who were SGA at birth showed a significant increased risk of unsatisfactory growth and need to auxological referral  were hospitalized again during the first year of life. Thirty-three children (41.25%) are in clinical follow-up because of minor problems not affecting feeding nor growth and 6 subjects (7.5%) have food allergies. Vaccination rate was high in the evaluated sample: 78 children (97.5%) were regularly vaccinated, 1 child was exempt due to severe immunodeficiency and only 1 had a delayed vaccination schedule. No socioeconomic problems were present in children’s families.In the first six months of life 53.8% of infants were exclusively or predominantly breastfed, 46.2% were exclusively formula-fed, using standard formulas for preterm and then for term infants in the great majority of cases. Average weaning time was 6.00±1.09 months. No infant followed special diets and 19 children (23.75%) were given food supplements  at the time of follow-up.ST size at birth Standards [p < 0.0001) when compared to routinely used size at birth charts, among whom Fenton charts [ST size at birth standards [The main findings of the present study were first, that the use of INTERGROWTH-21tandards ,10 and otandards  thereaftn charts  were chotandards ,10 harmotandards ,14, at lST size at birth standards [Finally, being born SGA on, INTERGROWTH-21tandards ,10 is prThis study was conducted on a population of preterm infants admitted to a special care neonatal unit, without chronic or major morbidities. Most the infants were moderate and late preterm, who were reported in literature to be a population at risk of growth impairment and adverse outcome later in life, even if not as much as the severely preterm infants ,8. ST Preterm Postnatal Growth Standards [For such a vulnerable group of infants, the growth during hospitalization and the prevalence of growth failure at discharge were evaluated. A longitudinal approach is advisable in order to assess the EUGR, which can be calculated in different ways, with the percentile loss between birth and discharge or 40 weeks postmenstrual age, whichever comes first, being the most credited. In our study, the employment of INTERGROWTH-21tandards  significtandards  widely utandards  Infants ST standards [The small percentile loss experienced at discharge was recuperated over time and the distribution of percentiles at recruitment (on WHO standards) was very close to percentiles at birth in our cohort. For this cohort of moderate and late preterm infants, who did not develop relevant morbidities over the follow-up period, WHO charts ,14 repretandards ,10,11, iFinally, a focus was put on SGA infants, who are known to be at increased risk of growth faltering and developing complications. ,20,21,22Recruited children did not show significant morbidities during follow-up, average weaning age was in line with guidelines and there was high adherence to vaccination schedule.The main strengths of the study were the relatively large sample if considered that reliable and accurate measurements were taken for all subjects at least at three time points, i.e., birth, term corrected age and preschool age; the study has a major novelty that relies in its extension not only up to term corrected age, but to preschool age, and validates the use of INTERGROWTH-21ST and WHO Child growth standards as a consistent tool to monitor growth in the first years of life for preterm infants; finally, the gestational age at birth range between 30 and 36 weeks allows a good focus on moderately and late preterm infants, thus excluding confounding factors such as extremely low gestational age with its known burden of comorbidities and nutritional challenges.Limitations of the study are the retrospective collection of obstetric antenatal data, the use at follow-up visits of questionnaires, which may be affected by recall bias and the fact that approximately one third of the intended preterm infant sample could not be included, for parental refusal or invalid phone numbers.The employment of INTERGROWTH-21st charts  during tThe implementation of a package of standards at birth, preterm postnatal growth standards ,10,11 anSize at birth neonatal standards ,10 identST existent charts, that are more reliable after 32 weeks of gestational age. Those infants are also more complicated to study because of frequent comorbidities and still debated nutritional strategies.The present study was conducted on a moderate and late preterm infants cohort: future studies focused on very preterm neonates may shed light on the growth monitoring of this high risk population, even if those infants are more difficult to be followed-up on INTERGROWTH-21


Infant birth weight influences numerous health outcomes throughout the life course including childhood obesity and metabolic morbidities. Maternal experience of stress, both before and during pregnancy, has been hypothesized to influence fetal growth and birth outcomes. However, these associations currently are not fully understood, due to conflicting results in the published literature. Salivary cortisol is often used as a biological biomarker to assess the diurnal pattern of the hypothalamic–pituitary–adrenal axis (HPA-axis) functioning. Cortisol metrics include both the total cortisol concentration secreted during waking hours, reflected by the area under the curve (AUC), and cortisol dynamics, which include the diurnal cortisol slope (DCS) and the cortisol awakening response (CAR). This study examined the association of these cortisol metrics measured during the third trimester of pregnancy and infant birth weight among 240 mother-infant dyads participating in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort study, which is predominately comprised of Hispanic low-income women. There were no significant associations with the maternal biological stress response and infant birth weight in this study. More research is needed in larger studies to better understand how the biological stress response influences birth weight in populations facing health disparities. Infant birth weight is an indicator of the intrauterine environment and is associated with numerous health outcomes throughout the life course ,2. Low bHealth disparities exist between racial/ethnic groups as well as income levels . Income Cortisol is a key hormone that is produced by the hypothalamic–pituitary–adrenal axis (HPA-axis), which is one of the major components of the physiological stress response system. Cortisol secretion follows a circadian pattern, with daily cortisol levels rising in the hours prior to awakening with a peak approximately 30 min after awakening, followed by a decline throughout the day and reaching the lowest levels in the late evening hours ,23,24. AIn order to further elucidate the relationship between maternal HPA-axis activity during pregnancy and fetal growth, we aimed to explore the association of the maternal biological stress response during the third trimester through several cortisol metrics. These metrics include the total cortisol concentration secreted during waking hours, reflected by the area under the curve with respect to ground (AUCg), and cortisol dynamics, which includes both the diurnal cortisol slope (DCS) and the cortisol awakening response (CAR). The DCS reflects the change in cortisol secretion from morning to evening while the CAR represents the increase in cortisol secretion specifically in the 30–45 min from awakening ,49. ThesAll participants were enrolled in the ongoing maternal and developmental risks from Environmental and Social Stressors (MADRES) pregnancy cohort study. The cohort is based in urban Los Angeles and is predominately comprised of Hispanic women, followed by a smaller sub-set of Black women. The majority of mothers are of low-income, primarily insured by Medicaid/Medi-Cal, which are strong indicators of health inequities. Methods of the MADRES study and protocol have been described previously . In brieN = 372) and completing quality control checks to ensure all samples were taken on the same day by individually looking at each mother’s reported times and dates, 343 mothers collected at least one sample according to the protocol (explained in more detail below). Three dyads were then removed for not having recorded birth weight available, seven dyads were removed for missing maternal demographic data and/or key covariates collected in the third trimester questionnaire, and 93 were removed for providing less than four saliva samples on the assessment day, which were needed to calculate the cortisol concentration of AUCg. The consort diagram presenting sample exclusions are shown in N = 343) to those who completed collection of all four samples across the day (N = 240).Within the MADRES cohort, 372 mothers completed at-home saliva collections over one day (up to four samples) in their third trimester of pregnancy (sample range: 26–35 weeks gestation). A total of 240 mother–infant dyads with complete maternal cortisol data, birth outcomes data, and key maternal and infant covariates were included in the current analysis. After cleaning the raw data  over a one-day period in their third trimester of pregnancy . Most participants completed this sample collection on a weekday (84.6%). Participants were instructed to gently chew on a cotton dental roll for two minutes at time of awakening, thirty minutes after awakening, in the afternoon (between 3–4 pm), and before bedtime. Participants were educated on the importance of following the protocol, and they were instructed to record the exact time and date that each sample was completed on the collection tube. The participants were also asked to mark if they ingested anything other than water, smoked, brushed their teeth, or exercised within the 30 min prior to collecting the sample. Non-adherence to this was flagged for possible contamination. These instructions were provided over the phone with the participant. In addition, each participant was also given a pamphlet with detailed yet easy to understand directions and pictures for each step. This pamphlet also included the contact information to a study staff member if any additional questions arose while completing the saliva collections.n = 240), 91.7% of participants completed the first sample within 15 min of waking up and 93.75% completed the second sample within 15–45 min of the first, reflecting high compliance. The collection time with the least reported contamination was for the awakening sample (2.5%), while the highest was seen in the afternoon sample (34.6%), mostly due to eating or drinking prior to collection. The samples that were outside of the instructed times, possibly contaminated, or larger than four standard deviations (2.8%) were flagged for additional sensitivity analyses.Within the final study sample . Saliva samples were then stored in a laboratory freezer at −80ºCelsius until they were sent to a commercial laboratory to be assayed for cortisol. They were then frozen and stored at −20ºCelsius until analysis. After thawing, Salivettes were centrifuged at 3000 rpm for five minutes, which resulted in a clear supernatant of low viscosity. Salivary concentrations were measured using commercially available chemiluminescence immunoassay with high sensitivity . The intra-assay and inter-assay coefficients for cortisol were below 9%.Cortisol levels measured in nanomoles per liter (nmol/L) for each time point were then converted into total cortisol concentration during waking hours reflected by the AUCg and cortisol dynamic variables . The AUCg was calculated using the standard trapezoidal formula, which requires all four samples to be complete and considers the time between sample collection and the cortisol level at each collection . Within For the majority of participants (97.5%), infant birth weight was directly abstracted from the electronic medical records (EMR). A small percentage of participants (1.7%) did not have physician measurements of birth weight recorded on the EMR but had a proxy report (mother) of birth weight noted on the EMR. The remainder of participants (<1%) did not have any birth weight recorded on the EMR, and birth weight was obtained from the mother via an interviewer-administered questionnaire with a MADRES staff member 7–14 days post-birth.Potential covariates were identified a priori based on previous literature and included factors related to study design, maternal demographics, and pregnancy and birth outcome variables. Preliminary analyses were then conducted for their univariate associations with the cortisol metrics  and birth weight. Study design variables included recruitment study site and gestational age (in weeks) at time of saliva sample collection.2). These variables were self-reported via interviewer-administered questionnaires in English or Spanish. The only exceptions were gestational diabetes status and preeclampsia status, which were both abstracted from the EMR (Yes vs. Not-Recorded), and pre-pregnancy BMI. Pre-pregnancy BMI was calculated using self-reported pre-pregnancy weight and standing height at the first study visit (<30 weeks gestation) measured by a study staff member via stadiometer (Perspectives enterprises model PE-AIM-101), or height from the EMR if missing. We did not use measured weight at the first study visit due to the range in weeks of gestation upon study enrollment.The maternal demographic covariates included: race, ethnicity (Hispanic vs. non-Hispanic), education level, annual household income, maternal age at baseline, personal smoking status during pregnancy, gestational diabetes status, preeclampsia status, and pre-pregnancy BMI . If unavailable, a second trimester (<28 weeks gestation) ultrasound measurement of fetal biparietal diameter was used (N = 68). If measurements from an early ultrasound were unavailable, gestational age at birth was calculated based on a physician’s best clinical estimate from EMR (N = 30). Delivery type and infant sex were abstracted from EMR; if these variables were missing from the maternal medical records, mode of delivery and infant sex were obtained via interviewer-administered questionnaires in English or Spanish 7–14 days after birth. Parity was self-reported via interviewer-administered questionnaire at the first study visit. Mother’s nausea was self-reported via interviewer-administered questionnaire during the third trimester in English or Spanish using the Pregnancy-Unique Quantification of Emesis (PUQE) scoring system. This scoring system enumerates the severity of nausea and vomiting during the preceding 24 h on a scale from 3 to 15. This was then dichotomized to mild nausea and vomiting  and moderate nausea and vomiting , as we had no mothers with severe scores (scores ≥13) [The pregnancy and birth-related covariates included: gestational age at birth (in weeks), delivery type , newborn sex, parity, and nausea experienced during the third trimester of pregnancy. Gestational age at birth was calculated and standardized using a hierarchy of methods . A firstres ≥13) .AUCg was right-skewed; therefore, values were log-transformed to decrease the influence of extreme values and to meet the linearity and homoscedasticity assumptions needed for linear regression. Analyses for DCS and CAR were performed on the original scale as these models met the assumptions of linear regression. Delivery type was dichotomized to vaginal or cesarean birth, and parity was modeled as first-born, second-born, third-born, or fourth-or-more-born.T-Tests were used with dichotomous covariates, which included infant sex, delivery type, personal smoking status, gestational diabetes status, preeclampsia status, PUQE nausea and vomiting, and ethnicity. Analysis of variance (ANOVA) was used with categorical covariates, which included race, parity, education level, and income level.We assessed the univariate relationships between all potential covariates with cortisol metrics  and infant birth weight. Pearson correlations were used with continuous covariates, which included GA at birth, GA at sample, maternal age, and pre-pregnancy BMI. Independent Student Within all multivariable models, infant sex, GA, maternal age, and ethnicity were deemed necessary due to their a priori importance in similar studies, as well as recruitment site as it is a crucial study design variable within MADRES. Confounding was then assessed by a beta estimate change larger than 10% for each individual stress metric by a one-by-one variable approach for all remaining covariates via linear regression. Confounding was observed by pre-pregnancy BMI and parity.After assessing the influence of a priori and possible covariates with stress metrics  and infant birth weight, the following variables were included in all multiple linear regression models: GA at birth, parity, continuous pre-pregnancy BMI, infant sex, maternal age at study entry, ethnicity, and study recruitment site. The selected covariates were then used in multiple linear regressions in three independent models, one for each cortisol metric variable . Sensitivity analyses were then conducted to determine whether results were similar after excluding preterm births (<37 weeks gestation). The significance level for analyses was set at an alpha of 0.05. All data were analyzed using SAS v9.4 .2. Their infants were born at a mean of 39 ± 1.5 weeks gestation and weighed on average 3302 ± 497 g at birth. The majority of infants were the first-born (35%) or second-born child (28%), and most were born vaginally (75%). Maternal smoking was not considered to influence birth weight in this sample, as the number of mothers who smoked at any point during the pregnancy was low .Maternal and infant characteristics are presented in The four salivary cortisol samples had the following mean concentrations: awakening sample 12.2 nmol/L, awakening +30 min sample 14.8 nmol/L, afternoon sample 5.7 nmol/L, and bedtime sample 4.0 nmol/L. These mean concentrations from the four salivary cortisol samples followed the expected daily circadian pattern of the HPA-axis and are shown in p = 0.25), log-transformed AUCg had an inverse relationship with infant birth weight after adjustment for covariates (B = −5.6 g for each 10% increase in non-logged AUCg). DCS had a positive relationship with infant birth weight after adjustment for covariates (β = 78.3); however, the association was not statistically significant (p = 0.08). CAR had no relationship with infant birth weight after adjustment . We tested whether the relationship between prenatal cortisol measures and infant birth weight was sensitive to babies born prematurely (<37 weeks gestation); however, our results were similar after excluding pre-term births in the analysis . However, that study averaged cortisol levels taken from one day over two trimesters in pregnancy and was in a Hispanic adolescent population, which may make results not fully comparable [p > 0.06), although the direction was not reported [r = −0.29, p = 0.05), with lower infant birth weight being related to a blunted cortisol slope in late pregnancy (34±1.4 weeks gestation); however, this association was seen in weeks later than our study and was insignificant  in weeks closer to our collection (28.1 ± 1.5 weeks gestation) [Although no significant associations were seen in this analysis, it is important to note that the beta estimates for the AUCg and DCS with birth weight were not close to zero. An inverse relationship was seen between AUCg and birth weight. This is in line with what Spicer et al. observed (mparable . Conversmparable . Bublitzreported . In contstation) .n = 55 and Spicer et al. n = 119) [Many strengths are found within the current study. This study measured salivary cortisol over four time points throughout the day, which allowed us to examine various cortisol metrics  to evaluate the association of the biological stress response with infant birth weight in a predominately Hispanic population. Evaluating the biological stress response in a population that is underrepresented in research and facing unique stressors as well as health disparities is an additional strength. This study was also conducted with a larger sample size relative to the literature, especially when compared to those with predominately Hispanic populations  ,43.N = 843), 62% of pregnant mothers came in for their third trimester visit (N = 519). Demographics of these 62% of participants are similar to the overall cohort. Of the 519 mothers that have completed the third trimester visit, cortisol collection participation for at least one sample was moderately high (72%). Lastly, although the cortisol samples were taken before birth in the third trimester, no other cortisol levels were available earlier in pregnancy. Therefore, the current study was unable to assess whether birth weight is more sensitive to cortisol fluctuations in other prenatal exposure periods. It is also possible that cortisol levels during the first or second trimester could have had more effect on the fetus’s birth weight. If so, this study would have missed the effects of the biological stress response due to only having cortisol levels collected in the third trimester.Limitations of the study include that participants completed cortisol collection at home and were responsible for marking the time of the sample, which could potentially introduce exposure misclassification. Assessing accurate cortisol patterns through salivary collection requires high compliance and motivation from study participants, which may be especially challenging in this population facing unique stressors. Raw data were vigorously checked for participant errors, lab errors, and data entry errors, and quality control steps were taken to reduce these errors as much as possible. It has additionally been suggested that at least two days of cortisol collection consisting of 3–6 samples per day are needed to appropriately capture the activity of the HPA-axis . It has Within this study of predominately low-income Hispanic women, there were no significant associations of the maternal biological stress response through cortisol concentration (AUCg) and cortisol dynamics (DCS and CAR) during the third trimester of pregnancy with infant birth weight. Although not significant, an inverse relationship was seen between AUCg and birth weight while a less steep DCS was seen to increase birth weight. Assessing accurate cortisol patterns through salivary collection requires high compliance and motivation from study participants, which may be especially challenging populations facing unique stressors. More research is needed in larger study samples with more rigorous approaches of cortisol collection including more sampling days, while also considering methods to increase compliance, to better understand how prenatal stress and the associated biological stress response influences birth weight.


To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer.  This was a retrospective study. Euthyroid patients undergoing the first fresh D3 embryo transfer from January 2018 to May 2019 were initially included. The patients were divided into a low-TSH (0.27–2.5 mIU/L) group and a high-normal TSH (2.5–4.2 Miu) group. The reproductive outcomes were compared between the groups. P = 0.416, 0.163, and 0.219). No significant differences were observed in terms of gestational age, single live birth rates, and birth weight, or birth length.  A total of 1786 women were ultimately included, in which 1008 of whom had serum TSH levels between 0.27 and 2.5 mIU/L and 778 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.92, 1.30, and 0.88 and  High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Further studies are needed to test whether the results might be applicable to a wider population. Subclinical hypothyroidism (SCH), which was common in clinical practise, was a subtle deficiency in thyroid function regardless of the elevated thyrotropin (TSH) level and normal free thyroxine FT4) level . There i level . A total of 2542 infertile women receiving fresh D3 embryo transfer in the Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University, from January 2018 to May 2019, were initially included. The women underwent standard controlled ovarian hyperstimulation (COH) with a downregulation protocol using a GnRH-agonist or an antagonist protocol according to the patients' conditions. For women with poor ovarian response, mild ovarian stimulation was offered. Oocytes were retrieved transvaginally 34–36 h after HCG administration and were inseminated using either the IVF or the ICSI method. Rescued ICSI was performed when necessary to avoid failure of insemination. Variable cleavage embryos were observed and scored accordingly on the third day after insemination. High-quality embryos were preferentially transferred to the uterus under the guidance of ultrasound.n = 361); the presence of overt or subclinical thyroid dysfunction (n = 366); and lack of essential data (n = 29). After exclusions, 1786 women were transferred with fresh D3 embryos at the first IVF/ICSI cycle and were divided into two groups based on preconception TSH levels . As euthyroid women with preconception TSH<4.2 mIU/L were included in this study, no further tests or treatments were provided to them after starting the ovarian stimulation. The study has been carried out in accordance with the Code of Ethics of the Declaration of Helsinki.Patients with the following criteria were excluded: previous embryo transfers . Clinical pregnancy was defined as the presence of the gestational sac and fetal heart activity following positive serum β-hCG. Early embryo loss was defined as the lack of visible gestational sac or fetal heart activity following positive serum β-hCG. Ectopic pregnancy was defined as a pregnancy that did not occur inside the uterine cavity. Miscarriage, which included early abortion, intermediate abortion, and late abortion, was defined as a pregnancy that did not result in delivery. Preterm birth was defined as a gestational age less than 259 days (37 weeks). Live birth was defined as the delivery of live babies. Low live birth weight was defined as the neonatal weight less than 2500 g.Pregnancy was defined as positive serum t test or the Mann–Whitney U test where appropriate. Categorical variables were expressed as numbers or percentages, and the chi-squared test or Fisher's exact test was used for comparisons of categorical variables where appropriate. Binary logistic regression was then used to evaluate the impact of preconception high-normal TSH levels on the clinical and obstetric outcomes. Data were analyzed using SPSS 22.0 statistical software. All P values less than 0.05 were considered statistically significant.Our primary outcomes were clinical outcomes, such as clinical pregnancy rate, early pregnancy loss rate, miscarriage rate, and live birth rate. The secondary outcomes were obstetric outcomes, such as the single live birth rate, birth weight, birth length, and gestational age. Continuous data are expressed as the mean (SD), and statistical comparisons were performed by either Student's P = 0.107, 0.126). The frequencies of insemination methods and number and high-quality of transferred embryos were similar in both the groups . No difference was noted in terms of the scheme of ovarian stimulation (P = 0.355).The flowchart of the included women is shown in P < 0.001), 1.76 (P < 0.001), and 0.66 (P = 0.002), respectively, while younger age had slightly but significantly positive effects on the clinical pregnancy, live birth, and miscarriage with adjusted ORs of 0.93 (P < 0.001), 0.91 (P < 0.001) and 1.12 (P < 0.001), respectively. Anyhow, high-normal TSH levels had no adverse impact on the abovementioned outcomes  (As shown in ctively) .P = 0.129). The preterm birth rates were similar between the two groups . The low-weight birth rates were also similar between the two groups . In addition, the gestational age and birth length of single live births were similar between the low-TSH and high-normal TSH groups , as were the gestational age and length of twin live births .We further compared obstetric outcomes between the low-TSH and high-normal TSH groups. Of the 1786 women included, 471 in the low-TSH group had live births, while 385 in the high-normal TSH group had live births . No signIn this retrospective study, we investigated the association between preconception TSH and the reproductive outcomes of 1786 infertile women undergoing the first fresh D3 embryo transfer at a university-affiliated hospital and found that a high-normal preconception TSH level (between 2.5–4.2 mIU/L) was not associated with lower odds of clinical pregnancy and live birth or higher odds of miscarriage. Neonatal outcomes were also comparable between low-TSH and high-normal TSH groups.Chen et al.  investigOur previous results were in agreement with other studies, which demonstrated that mildly elevated preconception TSH levels before treatment had no adverse impact on the clinical outcomes in infertile women undergoing intrauterine insemination (IUI) treatment . In addiSimilarly, Reh et al. used different TSH cutoffs in a large retrospective cohort study which included first-cycle IVF patients, and no differences in the rates of clinical pregnancy, delivery, or miscarriage were observed after adjustments were made for age . AghahosAccording to the molecular basis of TSH and thyroid hormone action during implantation and early development, thyroid hormone might be involved in endometrium preparation for pregnancy and initial trophoblast development, and thyroid hormones are essential players in the mechanisms regulating implantation and early fetal development . As a maIn contrast, Diana et al. claimed a detrimental effect of high-normal preconception TSH levels on the clinical outcomes of infertile women undergoing their first IVF cycle . DiscrepThere were also some limitations in this study. First, this was a retrospective study with data collected from a single center, and selection bias was inevitable. Second, we did not report the status of thyroid antibodies in infertile women, which might have a role in infertility and miscarriage. However, on the one hand, the existing data are controversial regarding whether thyroid antibodies are associated with infertility or adverse reproductive outcomes , 14, 20.We included infertile women as homogeneous as possible to minimize the bias that may lower the power of the impact of TSH on reproductive outcomes. We found that a high-normal TSH level did not significantly influence the reproductive outcomes of infertile women undergoing the first fresh D3 embryo transfer. Further studies are needed to test whether the results might be applicable to a wider population.


Mothers in low socio-economic conditions frequently have low birth weight infants. Inaddition Physically demanding work during pregnancy also contributes to poor fetal growth. During gestation a woman needs balanced nutrition for a healthy outcome. Women with inadequate nutritional status at conception are at greater risk of aquiring disease; their health usually depends on the availability and consumption of balanced diet, and therefore they are unlikely to be able to resist with their high nutrient needs during pregnancy. Therefore, the main purpose of this study was to assess the maternal risk factors associated low birth weight in public hospitals of Mekelle city, Tigray North Ethiopia, 2017/2018.P value of less than 0.05 was considered to declare statistical significance. Table, graphs and texts were used to present the data.Un-matched case-control study design was conducted among women who delivered in public hospitals of Mekelle city. Data was collected using a structured questionnaire through interview, direct physical assessment and medical record review of mothers. Sample size was calculated by Epi-info version 7.0 to get a final sample size of 381(cases = 127 and controls = 254). SPSS version 20 was used for analysis. Bivariate and multivariate logistic regression analysis was used to determine the effect of the independent variables on birth weight. Presence of significant association was determined using OR with its 95%CI. A Most of the mothers (70.1% cases and 43.7% controls) were housewives. This study showed that maternal age ≤ 20 years (AOR = 6.42(95% CI = (1.93–21.42)), ANC follow up (AOR = 3.73(95%CI (1.5–9.24)), History of medical illness (AOR = 14.56(95% CI (3.69–57.45), Iron folate intake (AOR = 21.56(95%CI (6.54–71.14)), Maternal height less than 150 cm (AOR = 9.27(95%CI 3.45–24.89)) and Pregnancy weight gain (AOR = 4.93(95%CI = 1.8–13.48) were significant predictors of low birth weight.The study suggests that inadequate ANC follow-up, preterm birth and history of chronic medical illness, maternal height, pregnancy weight gain, and Iron intake were. Were significant predictors of low birth weight. Health professionals should screen and consulate pregnant mothers who are at risk of having infants with LBW and ensure that women have access to essential health information on the causes of low birth weight. World Health Organization (WHO) defined low birthweight as weight at birth of less than 2500 g regardless of gestational age. This cut-off point is based on observations that newborns weighing less than 2500 g. are 20 times more likely to die than heavier babies . LBW canLow birthweight is caused by either due to preterm birth (born before 37 weeks of gestation) or the infant being small for gestational age  or a combination of both . Small fIn many cases, the exact causes of prematurity are unknown; but they may associated with high maternal blood pressure, acute infections, hard physical work, multiple births, stress, anxiety, and other psychological factors . MultiplMothers in low socio-economic conditions frequently have low birth weight infants. Inaddition Physically demanding work during pregnancy also contributes to poor fetal growth , 7. DuriMajority of low birth weight children have higher rates of subnormal growth, illnesses, and neurodevelopmental problems. These issues increase becuase the child’s birth weight decreases. Low birth weight infants are prone to have difficulties in cognition, attention, and neuro muscular functioning . WorldwiMajority of LBW births occur in low- and middle-income countries and especially in the most vulnerable populations. Regional estimates of LBW include 28% in south Asia, 13% in sub-Saharan Africa and 9% in Latin America but it is also a global concern, to some high-income countries  at public hospitals of Mekelle City, Tigray, Ethiopia from February to March 2018.Mothers who delivered normal birth weight neonates (2500–4000 g.) in public hospitals of Mekelle City, Tigray, Ethiopia from February to March 2018.For cases; low birth weight child (< 2500 g) singleton live birthsFor controls; Normal birth weight (2500-4000 g) singleton live birthsFor all cases and controls; Newborns with congenital anomalies and critically ill mothers were excluded from the study.n = 381.Double population proportion formula using Epi-info version 7.0 statistical package was used considering maternal height (≤ 150 cm) as main exposure variable, percent of exposure for controls 6.2%  . And an All public hospitals in Mekelle city  were included on the study. Both cases and controls were proportionally allocated to each hospitals by taking their average flow of deliveries for the last 3 month as a baseline. Averagely in 3 months there were about 1606 neonates delivered in those three public hospitals of Mekelle city. Among these 778 were in ACSH, 624 in Mekelle and 204 in Quiha hospital. All cases in each hospital were included consecutively until the required sample siz were obtained and controls were recruited using systematic random sampling by selecting the participants every 3rd interval [Fig. Low Birth weight.Maternal Socio-demographic factor .Maternal nutritional factors .Maternal obstetric and health –related factors .Maternal behavioral factors .Newborns who have birth weight (2500 g. -4000 g.)Mothers who delivered low birth weight neonate (< 2500 g.)Mothers who delivered normal birth weight neonates (2500–4000 g.)Birth interval is defined as the length of time between two successive live births.Data were collected using a structured English version questionnaire which was adapted from different literatures. The socio- demographic and behavioral maternal factors were collected through interview. Maternal anthropometric measurements like Height was computed through physical assessment and ANC, gestational age and any relevant medical illness were extracted through reviewing of mothers’ medical record for both cases and controls within the first 6 h of delivery. Data collectors were interviewed to all mothers for whom who have singleton live births all over the data collection period at the selected hospitals for both controls and cases. Birth weight of every child was measured using balanced seca scale and the scale was rounded to the nearest 50 mg..Pretest was conducted in Wukro Hospital on 5% (in 7 cases and 14 controls) of study participants which were not included in the study prior to the actual data collection period to test the clarity, consistency and completeness of the questioner. Six data collectors (BSc. midwives) two for each hospital and one supervisor (BSc. midwifery) were trained for 1 day on how to collect, interview and the overall objectives of the study by principal investigator. English version Questioner were changed in to local language (Tigrigna) then translated back in to English for analysis. Weighing scales were checked and adjusted at zero level for the validity of the measurement. Data were managed by using appropriate data entry in to SPSS version 20 software package and it was cleaned before analysis.p value of ≤0.2. A multivariate logistic regression was used to determine the effect of the independent variables on birth weight and to control possible confounders. In order to test the significance level and association of variables at 95% confidence interval (CI), adjusted odds ratio and p-value ≤0.05 were used. Tables, graphs and texts were used to present the data.Affter the data were codded and cleaned it was entered to SPSS version 20 for analysis. Descriptive statistics such as mean (+SD) were calculated to compare group variables.. In the Binary logistic regression model bivariate analysis was run to include variables as a candidate in the multivariate logistic regression at Ethical clearance was obtained from the Institutional Ethical Review Board of Mekelle University College of Health Sciences and support letter was given fromTigray regional heath bureau to the selected hospitals letting permission. As long as reviewing mothers card and assessing mothers immediately after delivery needs verbal informed consent and confidentiality was preserved by apprising data collectors to use codes instead of writing names of the respondents and assuring the consent of respondents before data collection inorder to maintain permission of the participants. The informed consent was also applied for the newbons and and young mothers. The verbal consent was obtained from a parent on behalf of the participants under the age of 16.A total of 381 (127 cases and 254 controls) newborns were included in this study making a response rate of 100%. The mean birth weight was about 1966.6 g (S.D ± 359.58 g) for cases and 3125.gm (S.D ± 384.86) for the controls. About 70.9 and 29.1% of the cases were Preterm and term respectively [Fig. Fifty three 41.7%) of the mothers of the cases and 180(70.9%) controls were found in the age group 21–35 years. The minimum and maximum age of both mothers of both the cases and controls were 15 years and 45 years respectively. About 85% percent of mothers of the cases and 81.5% of mothers of the controls were orthodox. Larger proportions of cases (70.1%) and controls (43.7%) were housewives. Fifty seven percent (57.5%) of cases and (69.3%) of the controls reside in urban area. [Table .7% of thAlmost half of the mothers of the cases (46.5%) and controls 42.5%) were primi-gravida. Most mothers of the controls (86.2%) and cases (81.9%) had no history of abortion. About 73(57.5%) of the cases had 1–2 ANC visits while 169(66.5%) of the controls had 3–4 ANC visits during their pregnancy. Fourty prcent of the cases and 16.1% the controls had pregnancy related complication in which PIH accounts 20.5 and 6.3% of the complications for cases and controls respectively. , Those mothers with 1–2 ANC follow up were three times more likely to have low birth weight baby than mothers having 3–4 ANC follow up (AOR = 3.73(95%CI (1.5–9.24)). Mothers who had history of medical illness were at risk to give low birth weight baby as compared to mothers with no history of chronic medical illness (AOR = 14.56(95% CI (3.69–57.45));Mothers who take iron folate < 60 were twenty one times more likely to deliver low birth weight babies than those who take > 90 tablets (AOR = 21.566.54–71.14)). Mothers with height < 150 cm were nine times more likely to deliver low birth weight baby than their counter part (> = 150 cm) with (AOR = 9.27(95%CI 3.45–24.89) and mothers who gain weight < 12 kg during pregnancy were at higher risk than those who gain > = 12 kg (AOR = 4.93(95%CI 1.8–13.48)).preterm babies were fourteen times more likely to be low birth weight than term babies (AOR = 14.28((95%CI = 5.75–35.47). (Table –71.14). LBW is still a significant cause of morbidity and mortality among neonates. This study has tried to assess determinants of LBW among mothers who gave birth at public hospitals of Mekelle city. Results of this study found that maternal age was a significant predictor of low birth weight. This result is in line with studies conducted in Brazil, India, and Bale , 14, 15.This study also revealed that mothers who did not follow ANC were three times more likely to have low birth weight baby than mothers who have 3–4 ANC follow up. This finding is in agreement with a study done in Eastern Nepal, Addis Ababa and Axum –18. ThisIn this study mothers who took < 60 iron folate tab were twenty one times more likely to deliver low birth weight babies than those who take > 90 tablets. This result is similar with studies conducted in Eastern Nepal and Tigray , 19. whiThis study revealed that Maternal height < 150 cm was found as significant predictor of LBW this is congruent with study done in Bale and India , 15. TheIn this study preterm baby were fourteen times more likely to be low birth weight than term babies this is similar with study done in Addis Ababa and Axum , 18. ThiPregnancy weight gain < 12 kg was another significant predictor of LBW .this is in line with study done in India . This miSince the design of this study is institution based case control study, it may have limited the generalizability of the findings to the community.Also, this study selectively addressed certain factors of low birth weight while various factors are found to cause the diseases.The study suggests that inadequate ANC follow-up, history of chronic medical illness, maternal height, pregnancy weight gain, and Iron intake were significant predictors of low birth weight. Health professionals should screen and counsel pregnant mothers who are at risk of having infants with LBW and ensure that women have access to essential health information on the causes of low birth weight. Mothers should receive problem (low birth weight) specific counseling by skilled health personnel with emphasis given to those with chronic medical illnesses prevention of preterm Nutritional education to improve the weight gain during pregnancy, and prevention and proper management of chronic medical illness.Additional file 1. Questionnaie Tsehay. Questionnaire. The data contains the questionnaire for collecting information on maternal risk factors associated with low birth weight. The questionnaire has four sections. The first section is concerned with datas related to newborn characteristics, the second section is concerned with socio demographic characteristics while the second and third sections are concerned with Obstetric and gynecological history and maternal nutritional factors respectively.


Background: Early nutritional support of preterm infants is important because it influences long-term health and development. Body composition has an influence on cardiovascular disease, metabolic syndrome, and neurocognitive outcome in the long term.Objective: To assess body composition in preterm infants <32 weeks of gestation at term-equivalent age and to analyze the influence of an optimized nutritional approach.Methods: This is a prespecified secondary outcome analysis of a prospective observational study comparing the body composition in regard to gestational age. The preterm infants were classified according to gestational age as extremely preterm infants (<28 weeks gestation at birth) and very preterm infants (≥28 weeks gestation at birth) and according to weight percentile as appropriate for gestational age and small for gestational age. Body composition was determined by air displacement plethysmography using the PEA POD. The preterm infants obtained nutrition according to the ESPGHAN 2010 Guidelines.Results: Seventy-four preterm infants were analyzed. The mean (SD) gestational age was 28.7 (2.4) weeks, and birth weight was 1,162 (372) g. Fat mass percentage was significantly higher in extremely preterm infants in comparison to very preterm infants . There was no significant difference of fat mass percentage according to weight percentiles.Conclusions: Extremely preterm infants had a significantly higher fat mass percentage compared to very preterm infants at term-equivalent age. There was no significant difference of fat mass percentage according to weight percentiles. Adequate early nutritional support of preterm infants is essential for long-term health and development . EspeciaThe aim of the study was to assess FM and FFM in very preterm infants (VPI) born ≥28 weeks in comparison to extremely preterm infants (EPI) born <28 weeks of gestation at term-equivalent age. The second aim of the study was to analyze the relationship between FM and weight percentiles in neonates, who received nutrition according to the ESPGHAN 2010 Guidelines , 14.This study is a prespecified secondary outcome analysis of a prospective observational study conducted at the Division of Neonatology, Medical University of Graz, Austria . PretermThe present analysis and PEA POD measurements were a standard procedure during the period of that nutritional analysis study . The stuBody composition was performed by air displacement plethysmography, using the PEA POD, Infant Body Composition System , which is an accurate and reliable technique considered as the international gold standard for non-invasive evaluation of body composition in infants , 17. TheTo measure whole body volume, the device is equipped with two chambers of identical volume, the test chamber, and the reference chamber separated by a volume-perturbing diaphragm sensitive to pressure changes. First, the PEA POD calculates the body surface area using the Boyd formula, which is then used to obtain the surface area artifact. The surface area artifact and the thoracic gas volume, which is a predicted value, are needed to correct the raw body volume, measured by the PEA POD. With these variables, body volume can be calculated. Electronic scales are included in the PEA POD to measure the infants mass. By using body mass and volume, the whole body density can be calculated. Fat mass can easily be calculated by knowing the density of fat, which is accepted as a constant of 0.9007 g/ml. The density of FFM changes during growth and depends on age and sex. The PEA POD uses age- and sex-specific density of FFM values, which are available in literature , 19. FatAt birth, infants were weighed using electronic scales . At body composition measurement, infants were weighed using the integrated scales of the PEA POD device. All measurements of length were performed using the SECA 210 Mobile Measuring Mat for babies and toddlers  .The local feeding protocol of the included preterm infants has previously been described in detail by Khan et al. . The prehttp://ucalgary.ca/fenton). The data from the individual measurements were collected in a Microsoft Excel spreadsheet and edited. Mann–Whitney U-Test and Kruskal–Wallis test was used in intergroup comparisons of categorical variables, and categorical variables were expressed as numbers and percentages. Multivariable linear regression was used to examine the association between the FM and FFM and the study groups with adjustment for the covariates: sex  born <28 weeks gestation and very preterm infants (VPI group) born ≥28 weeks gestation. For the second analysis, preterm infants were stratified according to their weight percentile  at the time point of birth and measurement, making up four groups . The classification was based on a publication of the ESPGHAN and on a consensus paper of the Austrian Society for Pediatric and Adolescent Medicine (ÖGKJ) , 23. To tes: sex  and gesttes: sex . Estimatn = 11), death before body composition measurement (n = 7), genetic disorder (n = 1), insufficient quality of measurement (n = 2), and loss to follow-up (n = 5)  . A total (n = 5) .In regard to growth percentiles, the infants were assigned to the following groups: AGA/AGA: 58 infants (78%); group SGA/SGA: 3 infants (4%), and group AGA/SGA: 13 infants (18%). No infant could be assigned to group SGA/AGA . Pretermp < 0.001). Weight and length at measurement were significantly higher in the EPI group than those in the VPI group, and there was no significant difference in weight z-score between the groups . There was no significant difference in length at measurement between the three groups. Weight z-scores at measurement were significantly lower in the SGA groups in comparison to the AGA group, as expected  had a significantly lower weight at measurement in comparison to the AGA group . FM and In this study, we analyzed the body composition in the EPI in comparison to that in the VPI at term-equivalent age. FM percentage was significantly higher in the EPI compared to that in the VPI group. The groups according to weight percentiles  showed no significant differences in FM. Infants born <28 weeks at gestation in comparison to infants born ≥28 weeks of gestation were discharged later. They had a significantly higher percentage of FM% at measurement.Mean FM% in the whole study cohort (15.9 SD 3.7) corresponds well to published data by Roggero et al. where mean FM% was 14.8 (SD 4.4) in preterm infants <1,500 g at term corrected age . Simon eThe preterm infants in the present study obtained nutrition according to the ESPGHAN 2010 Guidelines , 14, usiRoggero et al. published two studies including preterm infants <1,500 g. In these studies, FM% was higher in AGA preterm infants compared to SGA preterm infants (measured at term corrected age) , 39. VilThe strength of the study is the inclusion of extremely preterm infants and the relatively large sample size. Furthermore, we think that the number of patients represent a typical 1 year's cohort for a tertiary neonatal intensive care unit. There are some limitations to the present study, too. First, it is a single center study, and the number of SGA infants is small. Second, single point measurements are difficult to interpret; therefore, longitudinal measurements are of major interest for further studies. Furthermore, the aim of the present study was to investigate the FM% of preterm infants according to gestational age, but at the moment, it is unclear whether this will be the ideal parameter for assessment of neonatal growth. Other parameters might be of equal or even of higher relevance in the future, such as FFM% for instance.Rochow et al. recently published a longitudinal observational study where the FM% of preterm infants <32 weeks of gestational age [stratified in EPI (<28 weeks) and VPI (28–31 weeks)] had an impact on the neurodevelopment outcome at the age of 18 months. Ninety-six preterm infants received a Bayley III assessment at 18 months corrected age, showing that infants with a higher fat mass during hospitalization had a higher Bayley score . In addiThe higher FM% in EPI might indicate a higher risk for the development of adiposity and cardiovascular disease in later life, but the optimal body composition of premature infants at term-equivalent age is still unknown; therefore, we can only speculate about that.In conclusion, EPI had a significantly higher FM% compared to VPI at term-equivalent age. Preterm infants weight percentile at birth and the course to discharge had no impact on body composition. The nutritional regimen in our cohort seems to be adequate as in comparison to reference charts the mean FM% of the present study population was within normal range.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.The studies involving human participants were reviewed and approved by Ethics Committee of the Medical University of Graz, Austria. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.MB and BU: conception and design. MB, NM, and BW: collection and assembly of data. MB, ZK, CB, NM, and BU: analyses and interpretation of data. MB, CB, and BU: drafting of the article. MB, ZK, CB, NM, BW, SH, and BU: critical revision, editing, and final approval of the article.ZK received a scholarship for her Doctoral Studies from the Higher Education Commission (HEC) Pakistan and OeAD. Urlesberger Berndt was a member of the Advisory Board of Milupa/Danone. The remaining 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.