Objective Cesarean section (CS) delivery, especially without previous labor, is associated with worse neonatal respiratory outcomes. Some studies comparing neonatal outcomes between term infants exposed and not exposed to antenatal corticosteroids (ACS) before elective CS revealed that ACS appears to decrease the risk of respiratory distress syndrome (RDS), transient tachypnea of the neonate (TTN), admission to the neonatal intensive care unit (NICU), and the length of stay in the NICU.Methods The present retrospective cohort study aimed to compare neonatal outcomes in infants born trough term elective CS exposed and not exposed to ACS. Outcomes included neonatal morbidity at birth, neonatal respiratory morbidity, and general neonatal morbidity. Maternal demographic characteristics and obstetric data were analyzed as possible confounders.Results A total of 334 newborns met the inclusion criteria. One third of the population study  received ACS. The present study found that the likelihood for RDS , transient TTN , and NIUC admission  was higher in the ACS exposed group, although with no statistical significance. When adjusting for gestational age and arterial hypertension, the likelihood for RDS , TTN , and NIUC admission  become lower in the ACS exposed group.Conclusion Our findings highlight the known association between CS-related respiratory morbidity and gestational age, supporting recent guidelines that advocate postponing elective CSs until 39 weeks of gestational age. Cesarean section (CS) delivery, especially without previous labor, is associated with worse neonatal respiratory outcomes.There is evidence that the risk for CS-related neonatal morbidity is associated with gestational age, with higher risks in lower gestational ages.There is some evidence that, during labor, neurohormonal mechanisms involving the activation of sodium channels are responsible for alveolar fluid clearence.Studies comparing neonatal outcomes between term newborns exposed and not exposed to ACS before elective CS are sparse. Four trials  comparing prophylactic administration of betamethasone or dexamethasone versus placebo with usual treatment without steroids in term elective CS revealed that prophylactic ACS administration appeared to decrease the risk of respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), admission to the neonatal intensive care unit (NICU), and the length of stay in the NICU.Despite the promising findings in the aforementioned clinical trials, there is not sufficient evidence yet, regarding effectiveness or safety, to support the use of ACS in term elective CS. Unfortunately, the available guidelines for clinical practice are not coherent regarding this subject.We performed an observational retrospective cohort study.We selected all neonates delivered through elective CS between 37 0/7 and 38/7 weeks of gestation at the Hospital Divino Espírito Santo of the Ponta Delgada EPER between January 1, 2012, and December 31, 2017. All elective CSs were included regardless of the indication for elective CS or presence of maternal comorbidity/pregnancy complications. The exclusion criteria were: unknown pregnancy until time of birth, pregnancy with known congenital or chromosomic disorders, multifetal pregnancy, and mothers on systemic corticotherapy for reasons other than pulmonary maturation of the fetus. The charts of both mothers and newborns who met the inclusion criteria were reviewed by one of the three investigators.The present study was approved by the Hospital Divino Espírito Santo of the Ponta Delgada EPER ethics committee for health.We divided our population of selected newborns into two: (a) those exposed to ACS for pulmonary maturation; and (b) those not exposed. The decision of using ACS for lung maturation was made individually by the obstetric team.stand 5thminutes of life, need for oxygen supplementation, need for intermittent positive airway pressure (IPPV), and endotracheal intubation. Respiratory morbidity in the first 72 hours of life included: need for ongoing respiratory support , surfactant administration, and occurrence of RDS and TTN (as registered in the charts of the newborns).For primary outcomes, we evaluated the morbidity of the newborns at birth and the respiratory morbidity in the first 72 hours. Variables evaluating morbidity of the newborns at birth included: Apgar score (AS) at the 1Regarding secondary outcomes, we evaluated the occurrence of the following outcomes during hospital stay: need of a prolonged staying in the hospital (in days); need for admission at the NIUC; occurrence of hypoglycemia (documented glucose < 45 mg/dL); sepsis evaluation ; treatment with antibiotics for presumed sepsis; nutrition through nasogastric tube; and treatment for hyperbilirubinemia with phototherapy.stand 5thminutes of life. The composite respiratory morbidity outcome combines: the need of oxygen supplementation with need for noninvasive respiratory support; need for invasive respiratory support; need for surfactant therapy; and occurrence of RDS and/or TTN in the newborn. Finally, the composite general neonatal morbidity outcome combines: prolonged hospital stay (in days) with admission at the NIUC; nutrition through nasogastric tube; jaundice with need for phototherapy; sepsis evaluation; treatment with antibiotics; and hypoglycemia.Due to the expected low frequencies of the different outcomes in the study population, we also combined the various outcomes into three composite adverse outcomes. The composite morbidity at birth outcome combines: the need for oxygen supplementation with need for IPPV, need for EOT, and AS < 7 at the 1We also collected data regarding the drug use for pulmonary maturation (dexamethasone or betamethasone), the number of dosages taken by the mother – one or two for betamethasone and one, two, three or four for dexamethasone – and gestational age at the time of completion of the ACS cycle.Maternal demographic characteristics and obstetric data were also collected and analyzed as possible confounders, namely: age and race of the mother; prior maternal history of premature delivery; prior maternal history of cesarean delivery; maternal hypertensive disease ; maternal diabetes ; premature rupture of membranes; maternal history of hemorrhage during the first, second or third trimester; oligohydramnios; fetal growth restriction; and short cervix. Other data analyzed as possible confounders were birth weight and gender of the newborns.Data was analyzed using IBM SPSS Statistics for Windows, version 23.0 . Differences between groups for categorical variables were tested using either the χ2 or the Fisher exact tests. Multivariable logistic regression was also performed to estimate the odds for RDS, TTN, NIUC admission, prolonged hospital stay (≥ 5 extra days), and the composite morbidity outcomes in the ACS-exposed and not exposed newborns, adjusting for confounders with statistical differences between the two groups.n = 129; 38.6%) received ACS for pulmonary maturation. For these, the drug of choice was betamethasone in 81% (n = 94). The ACS cycle was completed in 93.7% (n = 104) of the exposed neonates. For those who completed the ACS cycle, the number of days between ACS and birth was < 2 days in 28.8% (n = 30), between 2 and 7 days in only 37.5% (n = 39), and > 7 days in 33.6% (n = 35). The main reason for elective CS in the present study , with the ACS-exposed group having more neonates born with gestational age < 38 weeks . Regarding the birthweight, only 6.5% of all newborns had low birthweight, with no statistical differences between groups (The majority of the study population (79.3%) had a gestational age ≥ 38 weeks . Howeve groups .p = 0,014; 95%CI), threatened preterm birth  and arterial hypertension , and composite general neonatal morbidity, the present study did not reveal a statistically significant difference even when adjusting for gestational age and arterial hypertension .There is not much available data regarding the rates of elective CS. It is believed that, due to the management of previous CS and breech presentation, elective CS has been increasing. Some studies report rates of elective CS of between 7.4 and 13%.Regarding obstetrical risk factors, our study revealed differences between the ACS-exposed and not exposed group in only 3 of the 12 variables included, namely: short cervix, threatened preterm birth, and arterial hypertension. We believe that some of these differences may represent confounding by indication that is, we believe that mothers received ACS based on their underlying risk profile.Regarding the outcomes regarding morbidity at birth, the overall incidence observed in the present study was very similar to those reported in the randomized cohort studies assessing ACS before an elective CS.Finally, according to the results of the aforementioned randomized cohort studies, prophylactic ACS appeared to decrease the risk of RDS , TTN , and admission to NICU for morbidity due to respiratory reasons , or any indication , and the length of stay in the NICU by 2.70 days .n = 65) of these fell outside the time window in which ACS are most effective. Finally, the retrospective nature of the present study warrants a careful interpretation of the results.Besides confounding by indication, some other limitations can partially explain the results encountered. One is the suboptimal exposure to ACS. It is known that the optimal window to birth is between 2 and 7 days after the ACS cycle.In conclusion, in elective CS between 37 and 38 + 6 weeks of gestation, there seems to be no differences regarding newborn outcomes between those exposed and not exposed to ACS. Therefore, the findings of the present study cannot support the use of ACS in this group. More studies regarding this topic, specifically prospective ones, are needed to validate this conclusion.


Demonstration of the management of a recurrent symptomatic hepatic cyst that was complicated by a buried lumen-apposing metal stent in the gastric antrum and a liver abscess. However, a minority of these cysts can cause symptoms related to abdominal pain, nausea, vomiting, or bloating. A larger cyst can lead to adverse events related to infection, spontaneous hemorrhage, compression of the biliary tree, or potential malignant transformation.A 65-year-old woman was referred for her fourth painful recurrence of a hepatic cyst. The 25-cm cyst was initially diagnosed in 1983, when she underwent a partial cyst resection and marsupialization. She remained asymptomatic until 2007, when she developed a painfully recurrent cyst measuring 8.5 cm. Surgical resection was unsuccessful and the cyst contents were bilious and mucoid, suggesting a possible cystadenoma of the wall, for which the lesion was ablated with alcohol. In 2010, surgeons were unable to mobilize a Roux limb to the liver; consequently, partial resection and cystogastrostomy were done to relieve the pain for up to 3 years. However, she developed recurrence of the cyst in 2014. Her fourth surgery attempt included a partial hepatectomy, cyst resection, marsupialization, and alcohol ablation, but these failed. She was then referred for endoscopic therapy.An initial attempt at EUS-guided cystogastrostomy in 2014 (with a non-cautery enhanced LAMS) resulted in severe bleeding after balloon dilation, with the cyst falling away from the gastric wall resulting in hemorrhagic shock and cardiac arrest from a bleeding left hepatic artery that was embolized. After a year of ongoing pain and resolution of a retroperitoneal hematoma, she requested another attempt at endoscopic drainage.On repeat EUS, the wall distance between the cyst and the gastric wall was less than 1 cm, and a 19-gauge needle was used to puncture the cyst again—this time closer to the antrum, where the surgical cystogastrostomy had been performed previously . A 0.035After being asymptomatic for 4 weeks, she developed a low-grade fever and pain. A CT scan showed an undrained portion of the cyst concerning for an abscess . A subseIdeally located, symptomatic hepatic cysts in nonsurgical patients can be treated with EUS-guided cystogastrostomy using a LAMS. One must drain all components of the cyst and be aware of the risk of buried LAMS in the antrum. Management of patients with a large symptomatic hepatic cyst should be carried out in a multidisciplinary setting. This case demonstrated that long-term relief of symptomatic cysts can be achieved with a cystogastrostomy. The procedure and indication require further study before being widely adopted, and the risk of life-threatening bleeding (as with any transhepatic puncture) should be discussed with the patient.Dr Irani is a consultant for Boston Scientific, CONMED, and Gore. Dr Canakis disclosed no financial relationships.


Are the changes in birthweight after frozen and fresh embryo transfer associated with corresponding changes in other measures of foetal growth and placental efficiency?Although placental efficiency was reduced for both frozen and fresh embryo transfer, children born after frozen embryo transfer (frozen-ET) had symmetrically increased size at birth, whereas children born after fresh embryo transfer (fresh-ET) were asymmetrically smaller at birth, compared to naturally conceived children.In pregnancies following frozen-ET, the risk of being born large, as measured by birthweight, is higher than after natural and fresh-ET conceptions. It is not known whether this is a result of symmetrically increased growth and increased placental efficiency.A Norwegian nationwide registry-based cohort study of 3093 singletons born after frozen-ET, 15 510 singletons born after fresh-ET and 1 125 366 singletons born after natural conception from 1988 to 2015 was performed. We identified 6334 sibships with at least two different conception methods.3), placental weight, birthweight:placental weight ratio, gestational age, and birthweight z-score. We estimated mean differences between children born after frozen-ET and fresh-ET compared to natural conception, at the population level and within sibships. Adjustments were made for birth year, maternal age, parity, and education.Data were collected from the Medical Birth Registry of Norway and the Norwegian National Education Database. Main outcome measures were birth length, birthweight, head circumference, ponderal index  and head circumference  at birth, but a similar ponderal index , compared to naturally conceived. Children born after fresh-ET had a shorter length  and head circumference , and lower ponderal index  at birth compared to natural conception within sibships. Furthermore, mean placental weight was larger after both frozen-ET  and fresh-ET  compared to natural conception within sibships, whereas mean birthweight:placental weight ratio was reduced for both frozen-ET  and fresh-ET . A range of sensitivity analyses all gave similar conclusions as the main models, including restriction to full siblings, restriction to single embryo transfer, and adjustment for maternal BMI, height, and smoking.Estimates at the population level and within sibships were consistent for all outcomes, for both fresh and frozen-ET compared to natural conception. Within sibships, children born after frozen-ET had longer mean length . Data on causes and duration of infertility, as well as treatment details, were limited.The increased birthweight observed in singletons after frozen-ET is associated with a symmetrically increased birth size and large placentas, also after controlling for maternal factors through sibship analyses. Identifying the responsible treatment factors and the long-term health outcomes are particularly important considering the increase in elective freezing of all embryos.This work was partly supported by the Central Norway Regional Health Authorities (project number 46045000), the Norwegian University of Science and Technology (project number 81850092) and the Research Council of Norway through its Centres of Excellence funding scheme (project number 262700). The authors have no conflicts of interest to declare.N/A. Children born after ART comprise an increasing proportion of birth cohorts in Europe . Over 30LGA can result from symmetric or asymmetric growth, defined by ponderal index at birth . Indeed,One distinct difference between fresh-ET and frozen-ET cycles is the supraphysiological hormone levels following controlled ovarian stimulation (COS) at the time of embryo transfer in fresh-ET , which was established in 1967, and collects information on all deliveries in Norway through a standardized notification form, completed by midwifes or doctors shortly after delivery. The MBRN collects information on maternal health before and during pregnancy, complications during pregnancy and delivery, as well as data on perinatal health. Ever since the first baby was born after IVF in Norway in 1984, MBRN has also collected information on ART treatment cycles resulting in ongoing pregnancies, directly from all ART clinics in Norway. The ART notification form contains information on mode of fertilization (ICSI/IVF), culture duration, and number of embryos transferred. Since 1988, information on embryo cryopreservation has also been recorded. After disclosure from the mother, midwifes also register ART-conception on the birth notification form, but details from the treatment will be missing. Following a revision of the delivery notification form in December 1998, information on maternal smoking and placental weight was included. Maternal height and weight have been recorded since 2007, but with a substantial proportion of missing data in the first years. The unique national identity number of each Norwegian resident was used to link information from MBRN to yearly information on education for women who gave birth during the study period, as recorded in the Norwegian National Education Database at Statistics Norway.3), head circumference at birth, placental weight, birthweight:placental weight ratio, and corresponding z-scores. To facilitate comparison with previous studies . Population level associations were estimated in random intercept models. Associations within sibships were estimated in models with a fixed intercept for each woman  . In the 2), and any smoking during pregnancy as a categorical covariate (yes/no). Estimates within sibships were not adjusted for maternal height, which is constant within sibships.We investigated the robustness of our data by restricting the main sample to relevant subpopulations. First, we restricted to mothers with two or more singletons with the same father (full siblings), to control for confounding by constant paternal factors such as ethnicity and height. Second, we restricted ART-pregnancies to those conceived after single embryo transfer. Third, we restricted analyses to only include deliveries with complete data on maternal height, pre-pregnancy BMI, and smoking (15% of main sample), and additionally adjusted for maternal height as a continuous covariate, BMI as a categorical covariate . Further, we adjusted for birth year, maternal age, and education, and obtained predicted means for each outcome.We evaluated the normality assumption of residuals using QQ-plots, density distribution plots and histograms. Assumptions were met for all outcomes.All statistical analyses were conducted using Stata Statistical Software, version 17 .The study was approved by the Regional Committees for Medical and Health Research Ethics (REK 2010/1909).3; NC: 28.0 kg/m3), reflecting shifts of population level distributions towards symmetrically larger sizes , birthweight (3611 g), and head circumference at birth (35.4 cm) compared to singletons after NC , reflecting shifts of population level distributions towards lower values , birthweight (3434 g), and head circumference at birth (34.9 cm) compared to NC , accompar values . Unadjusr values . Adjustmr values . In sensr values .z-scores of birth size gave results in the same direction as analyses based on direct measurements  compared to NC 675 g, , reflectAt the population level, fresh-ET had similar unadjusted mean (675 g) and distribution of placental weight as NC , but birz-scores of placental weight and birthweight:placental weight ratio gave results in the same direction as analyses based on direct measurements , which indicate that sample variations might drive inconsistencies with main findings rather than confounding. On the other hand, sensitivity analyses of full siblings were in line with main results, which control for constant parental factors. Although we cannot exclude confounding from non-constant factors, such as causes and duration of infertility, and parental changes in BMI, the consistency of results across order of conception method suggests that influence from such factors is limited. Furthermore, we had no data on treatment details, such as stimulation regimens, number of oocytes retrieved, embryo quality, culture medium, type of cryopreservation (i.e. slow-freeze or vitrification), or details on protocol for endometrial preparation in frozen-ET cycles .Pregnancies conceived in ART clinics outside Norway are only registered as ART-treatment if the mother discloses this to a midwife or doctor. Otherwise, they will be misclassified as a NC. However, this is unlikely to impact our results since they constitute a very small number compared to the large population of true naturally conceived pregnancies.Birth length measurement is delayed or not performed in deliveries with breech presentation, and the incidence of breech presentation is higher after ART  .Within-sibship analyses require at least two deliveries by each mother, and comparison with NC requires ability to conceive naturally. These women might be less infertile than women who conceive after ART in general. Despite comparable birth and placental size measures between the sibship sample and the full population, some caution is therefore needed in generalization to all ART pregnancies.The data used in this study are included in a recent Nordic sibship study of birthweight and gestational age . For both frozen-ET and fresh-ET, there was a reduced placental efficiency, as measured by birthweight:placental weight ratio compared to NCs.dead094_Supplementary_Figure_S1Click here for additional data file.dead094_Supplementary_Figure_S2Click here for additional data file.dead094_Supplementary_Figure_S3Click here for additional data file.dead094_Supplementary_Figure_S4Click here for additional data file.


Tarlov’s cyst is often underdiagnosed since it is difficult to identify without imaging assistance. Herein, we report the case of a young girl who presented with an 8-year history of chronic osteomyelitis of bilateral proximal phalanges and metatarsal bones caused by a Tarlov’s cyst that did not contain a nerve root. The chronic wound in the forefoot is an unusual presentation and resulted from the Tarlov’s cyst accompanied with tethered conus syndrome.A 10-year-old Asian girl presented with an 8-year history of chronic osteomyelitis of bilateral proximal phalanges and metatarsal bones. She received sequestrectomy five times, however the immune function tests were all normal. A neurological examination revealed diminished sensation and a slapping gait pattern. Magnetic resonance imaging (MRI) demonstrated a lobulated cyst at the right aspect of the sacrum (S) 1 to sacrum (S) 3 canal near the dorsal root ganglion. Tethered conus syndrome was highly suspected. She received laminectomy of lumbar (L) 5 and S1–S2, which led to the diagnosis of a right S1–S3 epidural cyst. The final diagnosis from the histopathological examination was a right sacral Tarlov’s cyst. The clinical conditions of diminished sensation and slapping gait pattern greatly improved after successful surgical treatment.In children who present with a recalcitrant chronic wound in the forefoot accompanied with a slapping gait pattern and foot hypoesthesia to pain, aggressive imaging examinations such as spine MRI should be arranged for further evaluation, especially in immunocompetent children.The online version contains supplementary material available at 10.1186/s13256-023-04232-1. Tarlov’s cyst, also known as perineural cyst, is a cerebrospinal fluid-filled sac. It usually forms on the extradural component of sacrococcygeal nerve roots at the junction of dorsal root ganglion and posterior nerve roots , and it A 10-year-old Asian girl presented with an 8-year history of chronic osteomyelitis of bilateral proximal phalanges and metatarsal bones. Since she at young age, she had been prone to fall easily since a young age, and she did not seem to be sensitive to pain. At one and a half years of age, she started to suffer from recurrent cellulitis on both big toes which was refractory to antibiotic treatment, although she was afebrile and had a slightly elevated white cell count and erythrocyte sedimentation rate. She had been gradually able to walk with assistance since she was 8 years of age. Furthermore, she had undergone sequestrectomy five times at 2, 3, 5, 7 and 9 years of age, respectively. As a result, her right big toe had been amputated due to persistent chronic osteomyelitis  8. Decreased height in T5 to T9 vertebral bodies. Arrowheads pointing the butterfly vertebra of thoracic 8.Additional file 2. Hypoplasia of posterior elements in L3 to L5 vertebrae. Arrowheads pointing the hypoplasia of posterior element.


The optimal method for human milk (HM) fortification has not yet been determined. This study assessed whether fortification relying on measured HM macronutrient content  composition is superior to fortification based on assumed HM macronutrient content, to optimize the nutrition support, growth, and body composition in infants born at <33 weeks’ gestation. In a mixed-cohort study, 57 infants fed fortified HM based on its measured content were compared with 58 infants fed fortified HM based on its assumed content, for a median of 28 and 23 exposure days, respectively. The ESPGHAN 2010 guidelines for preterm enteral nutrition were followed. Growth assessment was based on body weight, length, and head circumference Δ z-scores, and the respective growth velocities until discharge. Body composition was assessed using air displacement plethysmography. Fortification based on measured HM content provided significantly higher energy, fat, and carbohydrate intakes, although with a lower protein intake in infants weighing ≥ 1 kg and lower protein-to-energy ratio in infants weighing < 1 kg. Infants fed fortified HM based on its measured content were discharged with significantly better weight gain, length, and head growth. These infants had significantly lower adiposity and greater lean mass near term-equivalent age, despite receiving higher in-hospital energy and fat intakes, with a mean fat intake higher than the maximum recommended and a median protein-to-energy ratio intake (in infants weighing < 1 kg) lower than the minimum recommended.  Mother’s own milk (MOM) is recommended as the first choice for feeding preterm infants and donor human milk (DHM) is the best alternative when MOM is not available ,2. HumanTo prevent nutritional deficits in HM-fed preterm infants, while taking advantage of HM biological properties, HM multi-nutrient fortifiers are used, containing protein, carbohydrates, minerals, and vitamins, as well as some fortifiers containing fat ,10,11. TThe current literature indicates that very preterm infants at term age have a lower fat-free mass (FFM) and a greater fat mass percentage (%FM) when compared with term-equivalent-age (TEA) infants ,21,22. TCertain questions remain yet unanswered. First, despite many authors having considered target fortification as a more accurate method to achieve adequate intake of energy and macronutrients in preterm infants ,25,26, oIn a previous cohort study of preterm infants born at less than 33 weeks’ gestation fed standard fortified HM, we observed that the energy, protein, and fat intakes based on measured HM content were significantly lower than the intakes based on assumed HM content . FurtherThe aim of this study was to assess whether the newly implemented fortification method based on measured HM macronutrient content improves the energy and macronutrient intake and the quality of growth in infants born at less than 33 weeks’ gestation, compared with HM fortification based on assumed HM macronutrient content. Weight gain velocity was the primary outcome. In-hospital length and head growth velocities and body composition at late preterm or TEA were secondary outcomes.This is a single-center, observational mixed-cohort effectiveness study in preterm infants with less than 33 weeks of gestation . Energy Although the original design intended to compare, ‘per protocol’, the effects of standard and target HM fortification methods, as stated in the ClinicalTrials.gov NCT04400396 registry and the published protocol , additioThe study was approved by the hospital ethics committee (Nr 558/2018) and informed written consent was obtained from the parents or legal representatives of each infant. The study was conducted at the Centro Hospitalar Universitário de Lisboa Central, specifically in the Neonatology Unit and in the Human Milk Bank of Maternidade Dr. Alfredo da Costa, as well as in the Nutrition Laboratory of the Hospital Dona Estefânia.The eligibility criteria  were thoThe exposure period was defined by feeding fortified HM for at least 2 weeks. Recruited infants were dropped out if they were fed formula for two or more days with a >12.5% daily volume intake, or if they were transferred or deceased before completing the exposure period. The recruitment for the contemporary cohort of infants fed measurement-based fortified HM was initially planned to start in February 2020  to compare them with the historical cohort (2014–2015) of infants, who were fed fortified HM based on its assumed macronutrient content ,33. HoweThe required sample size was estimated to be 68 infants, with 34 infants in each group [As detailed elsewhere ,34, the Addition of a powdered, multi-component HM fortifier , containing 3.47 kcal of total energy, 0.25 g of protein, and 0.62 g of carbohydrates per g of powder, was started at a dose of 4.4 g/100 mL HM when the HM intake was at least 80 mL/kg/day. For fortified HM based on its measured macronutrient content, the MOM was analyzed once a week and the DHM was analyzed after pasteurization .The addition of modular protein and fat supplements to fortified HM was prescribed per clinical discretion, whatever the fortification method. According to the HM macronutrient content, a powdered modular protein , containing 3.38 kcal of total energy and 0.821 g of protein per g of powder, and/or medium-chain triglycerides , containing a total energy of 8.6 kcal and 0.95 g of fat per 1 mL, were added to the fortified HM, when necessary, in order to follow the ESPGHAN 2010 guidelines and reach the following target daily intakes for actual body weight: 110–135 kcal/kg of total energy, 4.0–4.5 g/kg of protein for infants with <1 kg body weight and 3.5–4.0 g/kg of protein for ≥1 kg body weight, and a protein-to-energy ratio (PER) of 3.6–4.1 for <1 kg body weight and 3.2–3.6 for ≥1 kg body weight . AlthougCollected variables: The recorded demographic variables included gestational age at birth, classified as ≥28 weeks or <28 weeks (extreme preterm); sex; singleton or twin; birth weight—small, appropriate, or large for gestational age  [ctively) ; severitctively) ; prenatactively) ; NEC (grctively) ; intra-pctively) ; multicyctively) ; and chrctively) .Analysis of HM macronutrient content: The HM samples were analyzed for macronutrient content using a real-time HM analyzer  [ Sweden) , followi Sweden) . The sta Sweden) . To miniAssessment of nutrient intake: The daily record of nutritional intake refers to feeds administered in the last 24 h. For each infant, the volumes of LH administered (MOM or DHM) were accurately recorded, considering the amounts actually administered, taking into account possible interruptions and gastric residual volumes. To calculate macronutrient (g/mL) and energy  densities of fortified HM, the macronutrient content of HM administered was recorded daily, as well as the macronutrient content of the added HM fortifier, modular protein, and MCT oil. The measured HM macronutrient content was used for calculations in the measured HM macronutrient content group and the estimated HM macronutrient content based on literature data [ure data  was usedure data .Anthropometry: Anthropometric parameters were assessed from birth to discharge. Body weight was measured by attending nurses at birth and daily during the hospital stay, with infants naked, using scales incorporated into the incubators or external automatic scales calibrated to the nearest gram [est gram . The weiest gram . In the est gram . These mest gram . Body composition assessment: A single body composition assessment using displacement plethysmography  was scheduled for up to one week after discharge for infants who maintained exclusive or predominant HM feeding. Fat mass (FM), FFM (%FM), and FFM percentage (%FFM) were provided automatically by the equipment. Using the aforementioned method, body length was measured by the same observer (MC), and this measurement was used to calculate the FM index (FMI) [ex (FMI) . The maiex (FMI)  and/or Fex (FMI) . The study sample size was calculated to detect a difference of 2 g/kg/day in weight gain velocity, the main outcome, with a significance level of 0.05 and 80% power; a required sample of 68 infants was estimated, with 34 infants assigned to each group  and 12.1The demographics and clinical characteristics of infants were described with frequencies (percentages) and with mean (SD: standard deviation) or median and interquartile range (IQR: 25th percentile–75th percentile), as appropriate. Nonparametric Chi-Square test, Fisher’s exact test, median test, and Mann–Whitney test were used, as needed.Univariable and multivariable linear regression models were used to identify the variables which explained the body weight, length, and head circumference z-scores at discharge, and between birth and discharge (Δ z-scores), and the variability of body composition. Normality assumption of the residuals was verified using the Kolmogorov–Smirnov goodness-of-fit test with Lilliefors correction.To study the association between independent variables and outcomes of excess adiposity (%FM > 95th percentile and FMI > 90th percentile), logistic regression models were used. For quantitative variables, logit linearity assumption (linear association with the logit of the outcome variable) was verified using generalized additive regression models.Additionally, in order to investigate associations between independent variables and weight, length, and HC gain velocities, linear mixed effects regression models were applied. Interaction terms were considered in the multivariable study.p-value ≤ 0.25 in the univariable analysis were candidates for the multivariable models.All the variables that attained a http://www.R-project.org, accessed on 5 January 2023).A level of significance α = 0.05 was considered. Data analysis was performed using Stata  and R . The reasons for lost to follow-up were formula feeding in 64 infants and hospital transfer before completing the study exposure period in 6 infants. Therefore, 115 completed the study exposure period, 57 in Group 1 and 58 in Group 2. No significant differences were found between the infants completing the exposure period and those who were lost to follow-up regarding gestational age, birth weight z-score, twin prevalence, extreme prematurity, prenatal and postnatal steroids, severity risk, late-onset sepsis (LOS), NEC, intraventricular hemorrhage, bronchopulmonary dysplasia, and hospital stay. An exception was a higher severity risk in infants who were lost to follow-up   dropped-out in Group 1 and 12 (17.1%) in Group 2 (= 0.026) .No significant differences were found between groups regarding demographic characteristics, birth weight, and morbidity, except for the infants of Group 2, who had a significantly higher prevalence of twins and LOS, and were significantly shorter and had lower head circumference at birth .The extremely preterm infants had a significantly higher severity risk, prevalence of LOS, and bronchopulmonary dysplasia than those who were born with more than 28 weeks’ gestation .25; P75) percentage of MOM volume administered during the hospital stay was 96.0%  for Group 1 and 96.5%  for Group 2. In both groups, the great majority of infants were fed MOM and a minority were fed DHM. The median (Pp = 0.072). No significant differences existed between the two groups in the postnatal age and PMA at the beginning or end of exposure, in time intervals before exposure, and from the end of exposure to discharge, in the percentage of days of exposure in relation to the total days of enteral feeding, and the total days of hospital stay . In partp < 0.001).A significant negative correlation was found between gestational age at birth and the number of days of exposure . Whatever the fortification method, an increase in length z-score from birth to discharge was significantly associated with an increase in body weight z-score from birth to discharge .In the multivariable analysis, no significant association was found between the body weight Δ z-scores from birth to discharge and the method of HM fortification (p = 0.023) and from beginning of fortification to discharge . This comparison considered only the weight gain velocity estimates at the time of discharge.By using the Patel method, the median weight gain velocity was significantly higher in infants fed fortified HM based on its measured macronutrient content than those fed fortified HM based on its assumed macronutrient content, both from birth to discharge . This result is in line with the graph shown in p = 0.007) and faster in infants born at or above 28 weeks’ gestation . This means that for each additional day of exposure, a mean decrease of 0.070 g/kg/d in weight gain velocity occurred, and infants born at or above 28 weeks’ gestation gained weight at a mean velocity of 7.6 g/kg/d faster than extremely preterm infants.Using a linear mixed effects model that considered daily estimates of weight gain velocity from birth to discharge, no association was found between them and the method of HM fortification  and with the decrease in the deviation of the body weight z-score from birth to discharge .The multivariable analysis showed that a smaller decrease in mean length z-score variation from birth to discharge was associated with the measured-based HM fortification method  using the fortification method based on measured HM macronutrient content.In the multivariable analysis, adjusted for gestational age, length gain velocity from birth to discharge had a significant positive association with the fortification method, with a faster mean increase of 0.20 cm/week , the fortification based on measured HM macronutrient content was significantly associated with a mean increase in the HC z-score from birth to discharge .In the multivariable analysis, adjusting for the length z-score variation from birth to discharge  using the fortification method based on measured HM macronutrient content, adjusted for gestational age, HC z-score at birth, and length of stay.In the multivariable analysis, the HC gain velocity from birth to discharge was significantly positively associated with the fortification method, with a faster mean increase of 0.18 cm/week  infants after discharge, between 35 and 41 PMA: 38 in Group 1 and 36 in Group 2. The reasons that precluded body composition assessment were mainly due to the temporary closure of the Nutrition Laboratory, which occurred due to the COVID-19 pandemic, and parental refusal in the remaining cases.p = 0.015), despite LOS not differing significantly between the HM fortification methods.No significant differences were found between infants with and without body composition assessment regarding gestational age, birth weight z-score, twin prevalence, extreme prematurity, prenatal and postnatal steroids, severity risk, intraventricular hemorrhage, bronchopulmonary dysplasia, NEC, and hospital stay. However, infants without body composition assessment had a higher occurrence of LOS  were HM fortification method, number of days of exposure, gestational age at birth, and mean energy, protein, carbohydrate, and fat intakes.p = 0.053). No multivariable models were found for excess adiposity.In the univariable logistic regression for the outcome of excess adiposity (%FM > 95th percentile), considering the fortification based on assumed HM macronutrient content as a reference category, weak evidence was found that infants fed fortified HM based on its measured macronutrient content had 74% lower odds of excess adiposity  with standard non-individualized HM fortification on growth, infants fed individualized fortified HM had a length gain velocity 0.3 cm/week faster during the intervention . This isThe HC measurements reflect brain size and head growth, which is an important indicator of neurodevelopment outcomes in preterm infants ,65.Infants in both groups were born with negative HC z-scores. In the fortification group based on assumed HM macronutrient content, HC z-scores declined up to discharge. Despite the fact that the infants fed fortified HM based on its measured macronutrient content were born with significantly lower mean HC z-scores, their HC z-scores increased up to discharge, attaining a higher mean z-score than in the infants fed fortified HM based on its assumed macronutrient content. Consistently, the multivariable analysis revealed that the increase in HC z-scores from birth to discharge was significantly associated with the fortification based on measured HM macronutrient content, adjusted for length z-score variation in the same period.The HC gain velocity was significantly associated with fortification based on measured HM macronutrient content, adjusted for gestational age, HC z-score at birth, and length of stay, and was 0.18 cm/week faster than using fortification based on assumed HM macronutrient content. In the aforementioned systematic review, preterm infants fed individualized fortified HM had, during the intervention, an HC velocity 0.10 cm/week faster than the standard non-individualized fortified HM .In a systematic review with meta-analysis, it was concluded that preterm infants at TEA have greater %FM and less FFM than those of infants born at term . This inThe body composition assessed after discharge at late preterm or term PMA (35 to 41 weeks) showed, via univariable analysis, that infants who had been fed fortified HM based on its measured macronutrient content had significantly lower fatness, as indicated by FM and adiposity (%FM and FMI), and greater leanness, as indicated by %FFM, compared with those fed fortified HM based on its assumed macronutrient content. In the univariable logistic regression, weak evidence was found that the infants fed fortified HM based on its measured macronutrient content had lower odds of excess adiposity; no multivariable models were obtained, rendering it impossible to control for other variables reported to affect fatness. This greater %FFM in infants fed fortified HM based on its measured macronutrient content is consistent with their faster linear growth, another indicator of lean mass . This isThese results for body composition raise two questions. First, why did infants who were fed fortified HM based on its assumed macronutrient content and receiving lower than recommended energy and fat intakes had greater adiposity at near TEA compared with those fed fortified HM based on its measured macronutrient content who received higher energy and fat intakes? Second, why did infants who were fed fortified HM based on its measured macronutrient content had lower adiposity and greater leanness at near TEA after receiving in-hospital energy and protein intakes according to ESPGHAN 2010 guidelines , but meaWe speculate that a mechanism could justify these findings. It has been described that in very preterm infants, postnatal age and PMA are strong predictors of FM and %FM at 34–37 weeks PMA . As the Certain limitations of this study should be acknowledged.This is an observational study that assessed the effectiveness of two methods of HM fortification in real-life clinical practice, where nutritional prescription was at the clinical discretion of physicians. The findings of this study do not substitute those of a randomized clinical trial assessing the efficacy of evaluated nutritional strategies.Infants lost to follow-up had significantly higher severity risk than those completing the study period. On the other hand, infants fed fortified HM based on its measured macronutrient content were born significantly shorter and with lower HC and had significantly higher severity risk, prevalence of twins, and LOS than infants fed fortified HM based on its assumed macronutrient content. Although these latter differences may be biases, they did not preclude the group fed fortified HM based on its measured macronutrient content from having better growth outcomes despite having more unfavorable factors.To accurately accomplish what the study set out to do, with recommendations for enteral nutrition in preterm infants, the ideal would have been to guide fortification based on daily analysis of MOM composition, but such frequency of analysis would be impractical as it would be overly laborious and time consuming ,28. MoreBody composition was based on a single assessment soon after discharge, rather than providing insight on previous changes and their relationship to in-hospital nutritional support. Nevertheless, our data can be compared with those from most other similar studies, which have focused on the body composition of preterm infants at TEA ,70.In the contemporary cohort, including the entire sample of fortification based on measured HM macronutrient content and part of the sample of fortification based on assumed HM macronutrient content, nutrient intakes were accurately recorded daily by the same observer and the amounts of modular protein and fat supplements added to the fortified HM were accurately calculated using a specifically developed informatics tool.Growth assessment during the hospital stay relied on weight, length, and HC Δ z-scores and their velocities, which are considered the better metrics to evaluate growth in preterm infants.To estimate weight gain velocity, in addition to using an accurate exponential method, which is superior to the conventional two-point assessment method, refined linear mixed effects regression models that consider the correlation structure between longitudinal measurements were used to analyze those estimates, providing differentiated results.A better body composition profile was found associated with mean fat higher than the maximum intake recommended and median PER (in infants weighing < 1 kg) lower than the minimum intake recommended by the contemporary ESPGHAN 2010 guidelines . ImportaIn this cohort study of infants born at less than 33 weeks of gestation, those fed fortified HM based on its measured macronutrient content had significantly better weight gain, length, and head growth at discharge, and lower adiposity and greater lean mass at or near TEA. This body composition profile was associated with energy and protein intakes in the range of the ESPGHAN 2010 guidelines but mean fat higher than the maximum intake recommended and median PER (in infants weighing < 1 kg) lower than the minimum intake recommended. These nutrient intakes were later revealed to be within the range of the updated ESPGHAN 2022 guidelines.Further high-quality trials are needed to confirm if the enteral nutritional regimen used in this observational study is more appropriate for better growth and body composition in preterm infants.


N = ∼12,000) using generalized additive models (GAMs). We observed that average height of the mothers increased by ∼4 cm across 60 birth years and that average birth weight of their children shows a similarly shaped and upward trend 28 years later. Our final model  revealed a significant and almost linear association between maternal height and birth weight. Maternal height was the second most important variable modeling birth weight, after gestational age. In addition, we found a significant association between maternal height and aggregated average height of males from the same birth years at time of conscription, 19 years later. Our results have implications for public health: When  height increases due to improved nutritional status, size at birth—and subsequently also the height in adulthood of the next generation—increases as well. However, the directions of development in this regard may currently differ depending on the world region.Changes in growth and height reflect changes in nutritional status and health. The systematic surveillance of growth can suggest areas for interventions. Moreover, phenotypic variation has a strong intergenerational component. There is a lack of historical family data that can be used to track the transmission of height over subsequent generations. Maternal height is a proxy for conditions experienced by one generation that relates to the health/growth of future generations. Cross-sectional/cohort studies have shown that shorter maternal height is closely associated with lower birth weight of offspring. We analyzed the maternal height and offspring weight at birth in the maternity hospital in Basel, Switzerland, from 1896 to 1939 ( We believe that our historical data exemplify the temporal dynamics of a maternal (height) effect on the offspring phenotype. We add to the existing literature on the intergenerational transmission of wealth and temporal trends in body height by drawing attention to an important aspect of intergenerational dynamics, namely maternal height. When  height increases in one generation due to improved nutritional status, the height of subsequent generations increases too. In the context of current developments, the trend toward smaller children at birth, which has been observed in many rich countries over the past few decades, could have an impact on current and future trends in adult size. However, the development in this regard may differ depending on the world region.Since the 19th century, average body height has steadily increased in many parts of the world . We brinFactors that are associated with growth and adult height include both genetics and the environment  . The intThe intergenerational effects of the parental phenotype are fundamental for various stages of growth  . AccordiHeight trends are most evident in intergenerational comparisons, with parents passing their improved health and height on to their children , 34–36. N = 12,107 mother–child pairs transcribed from birth records from the maternity hospital in the city of Basel, Switzerland, for the years 1896–1939  increase of ∼4 cm in the average height of the mothers born between 1860 and ∼1920  is also displayed in Fig. P < 0.0001) upward trend to maternal height ∼28 birth years earlier. Table P < 0.00001) effect on increasing adult male height , the genetic influence may be considerably lower , 102. InOur study has several limitations: We only know the average adult height of male offspring at 19 years of age, born in the maternity hospital thanks to published aggregated data from conscription, which also includes the male offspring of mothers who gave birth outside of the maternity hospital. Information on adult height for the female offspring is completely missing. As the historical Swiss conscription data have very high coverage  , 104, thCross-sectional studies have been the main source of documentation of secular trends in average height, mainly for males . We add We believe that our historical data exemplify the temporal dynamics of a maternal (height) effect on the offspring phenotype . HoweverAs shown elsewhere , 111, duWith the exception of the First World War, conventional measures of living standards  show a continuous rise in general wealth in Basel during the period 1895–1940 , 114. SkWe make use of a historical birth-weight database, which was transcribed and developed in the course of a completed Swiss National Science Foundation project (No. 156683) , 46, 111Founded in 1868, the maternity hospital was also a teaching hospital . ThroughOn the whole, the time period under consideration witnessed a rising standard of living with increasing real wages and decreasing infant mortality and stillbirth rates Fig. . The advNearly all birth records were linked to another register by means of a continuous and unique entry number (inventory Sanität X8). From this second register, additional variables regarding the socioeconomic background of the father (if known) are available. The occupations were classified by SEP as proposed by Schüren . We usedDespite extensive archival research, we have not been able to find an official measurement protocol from the maternity hospital for anthropometric measurements such as birth weight or maternal height. There is also no reference to these measurement procedures in other reports of the hospital. The exact measurement practice must therefore remain uncertain and could have changed over time as well as between measuring persons. The distribution graphs of birth weight and maternal height Fig.  suggest,We linked variables about the father (if known) from the birth register to variables about the mothers and their offspring found in the birth records see . We usedN = 13,988), we excluded the years 1901 and 1902, since only first parities were transcribed in those 2 years . We also excluded births for which the maternal year of birth was 1917–1919, because only a few births were recorded for these values . Multiple births , stillborn neonates , mothers aged <20 years , missing birth weight , missing parity , missing maternal age , missing newborn sex , and missing gestational age  were excluded as well, resulting in a sample size of N = 12,107 . In order to estimate how tall the newborn males had grown by the time they were recruited at age 19, we used published mean values  , 124. Byk = AICk − AICM. The larger ΔAICk is, the greater the importance of the variable in the model.In order to explore the importance of each independent variable on the outcome, each independent variable was dropped from the model one at a time and the AIC of the model was computed. We then computed the difference between the AIC for the complete model M and the model with one independent variable k removed, i.e. ΔAICR version 4.2.1 was used for all statistical analyses. The package “mgcv”  was usedpgad208_Supplementary_DataClick here for additional data file.


To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes .Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy.Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers  and infant birth weight  such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission .There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress. Adverse birth outcomes, including low birth weight and preterm birth, are a serious public health concern given their association with short- and long-term negative health consequences for mothers and children . Short gResearchers have proposed various conceptual models to explain how maternal exposure to childhood adversity may influence later risk for adverse birth outcomes. According to the pathway perspective of life course health proposed by Hertzman , early aFinancial stressors  during pregnancy are common in the United States. From 2013 to 2018, 60% of peripartum mothers reported healthcare unaffordability and 54% reported general financial stress . These rThe goal of the present study was to test whether maternal exposure to ACEs is indirectly associated with three birth outcomes  through financial stress during pregnancy. We hypothesized that a higher maternal ACE score would be associated with greater financial stress during pregnancy, which would be associated with a greater likelihood of NICU admission, earlier gestational age at birth, and lower infant birth weight.Pregnant women (n = 577) were enrolled between April 2018-March 2020 in two cohorts—the Stress and Health in Pregnancy (SHIP) cohort in North Carolina and the Prospective Research on Early Determinants of Illness and Children’s Health Trajectories (PREDICT) cohort in Florida. Both cohorts enrolled from university-affiliated obstetric clinics. Women were eligible if the mother was > 18 years old, spoke and read English (PREDICT), or English or Spanish (SHIP), and planned to deliver at the study-affiliated hospital. Women were ineligible if the fetus had a known congenital anomaly or chromosomal abnormality, or if the mother had HIV, Hepatitis C, or Hepatitis B. Average gestational age at enrollment was 20.8 weeks (SD = 6.9) for SHIP and 24.6 weeks (SD = 6.3) for PREDICT. After enrollment, women completed questionnaires about demographics and health behaviors and provided obstetric, medical, and social histories. Maternal obstetric and infant delivery records were abstracted following delivery. The SHIP study was approved by the Institutional Review Board (IRB) at North Carolina State University, and the PREDICT study was approved by the IRB at Johns Hopkins All Children’s Hospital. Mothers provided written informed consent for themselves and their children. In the present study, 12 mothers who gave birth to multiple children  were removed from analyses, in addition to eight cases due to intrauterine fetal demise and 14 mothers who reported a race other than Black or white. Thus, the analytic sample for this study included 531 mother-infant dyads.Mothers reported on their ACEs during the first study visit  using the 10-item measure developed by Felitti et al.  that assFinancial stress was also measured during the first study visit using the 6-item Financial Stress Index , 38], w, w38], wInfant birthweight, gestational age at birth, and NICU admission during the initial delivery hospitalization stay were preferentially extracted from hospital delivery records (admission to the NICU following delivery discharge was not included). In the few cases where these data were missing (n = 9), maternal reports of gestational age were obtained at six weeks postpartum.Covariates included study cohort, maternal pre-pregnancy body mass index , self-reported tobacco use during the pregnancy (yes/no), race , and ethnicity (Hispanic/Latina or not Hispanic/Latina).p < 0.001), suggesting that data were not missing completely at random; however, visual inspection of the patterns of data did not reveal substantial differences between those with and without data on these variables. Given this, and the minimal amount of missing data, we assumed data to be missing at random and imputed missing data using pairwise deletion for our binary outcome (NICU admission) and full information maximum likelihood estimation for our continuous outcomes .All analyses were conducted in R version 4.1.3 . Prior tlavaan  = 0–2), with similar exposure to childhood adversity across cohorts. On average, mothers in both cohorts reported low amounts of financial stress during pregnancy ; average infant gestational age at birth was 38.63 weeks, which is considered early term, and 12% of babies were admitted to the NICU.Demographic and study characteristics are shown in Table We conducted a series of mediation analyses to test the direct and indirect association between maternal exposure to ACEs and several birth outcomes through financial stress during pregnancy. Table b = 0.63, 95% CI = 0.39–0.92), though there was no evidence of an association between maternal ACE score and NICU admission  or financial stress and NICU admission . There also was no evidence of an indirect association between maternal ACE score and NICU admission through financial stress . These results were robust to removal of outliers.First, we tested whether maternal exposure to ACEs was associated with NICU admission directly, as well as indirectly through financial stress during pregnancy. Higher maternal ACE score was associated with greater financial stress during pregnancy , though there was no evidence of an association between maternal ACE score and gestational age . Mothers’ financial stress during pregnancy was inversely associated with gestational age at birth , and there was an indirect association between maternal ACE score and gestational age through financial stress  such that a higher ACE score was associated with earlier gestational age through increased financial stress during pregnancy. These results were robust to removal of outliers.Next, we tested whether maternal exposure to ACEs was directly associated with gestational age at birth, and indirectly through financial stress during pregnancy. Higher maternal ACE score was associated with more financial stress , though there was no association between maternal ACEs and birth weight . Mother’s financial stress during pregnancy was inversely associated with infant birth weight , and there was evidence of an indirect association between maternal ACEs and birth weight through financial stress . These results were robust to removal of outliers.Lastly, we tested whether maternal exposure to ACEs was directly associated with birthweight, and indirectly associated through financial stress during pregnancy. Higher maternal ACE score was associated with greater financial stress during pregnancy  child tax credits, extension of Medicaid coverage from 60 days to a full year post-partum , paid paThe present study had several strengths, including a racially and ethnically diverse sample of expecting mothers and temporal ordering of events that aids in establishing causation. There are, however, several limitations to consider when interpreting these results. First, we were not able to adjust for all possible confounders, namely mother’s childhood socioeconomic status, which presents a major potential confounder of the exposure-mediator and exposure-outcome relationships . Second,Our study findings suggest that maternal exposure to ACEs increases risk for adverse birth outcomes  through increases in financial stress during pregnancy. Existing interventions and policies can be implemented to better serve mothers exposed to childhood adversity who may be at risk for financial strain during pregnancy. Future studies that focus on specific aspects of financial strain  and mechanisms  linking financial strain to these adverse outcomes will paint a clearer picture of the intergenerational transmission of stress and ways to improve the health of children at the earliest stages of development.


The Juno Waves instrument measured plasma waves associated with Ganymede's magnetosphere during its flyby on 7 June, day 158, 2021. Three distinct regions were identified including a wake, and nightside and dayside regions in the magnetosphere distinguished by their electron densities and associated variability. The magnetosphere includes electron cyclotron harmonic emissions including a band at the upper hybrid frequency, as well as whistler‐mode chorus and hiss. These waves likely interact with energetic electrons in Ganymede's magnetosphere by pitch angle scattering and/or accelerating the electrons. The wake is accentuated by low‐frequency turbulence and electrostatic solitary waves. Radio emissions observed before and after the flyby likely have their source in Ganymede's magnetosphere. Whistler‐modes, electron cyclotron harmonics, upper hybrid band and radio emissions are detected in and near Ganymede's magnetosphereThree distinct regions in and near the magnetosphere are observed, wake, nightside, and daysideThe dayside ionosphere exhibits higher and more variable electron densities than does the nightside The +z axis is parallel to Jupiter's rotational axis and the +x axis is parallel to the nominal co‐rotational plasma flow. The +y axis is in the direction of Jupiter. The radius of Ganymede (RG) is 2,631.2 km. The blue, green, and red bars denoted with the numbers 1, 2, and 3 identify regions observed in Ganymede's magnetosphere and will be used to organize the discussion of the Waves observations.The Juno spacecraft executed a close flyby of Ganymede at 16:56 on 7 June, day 158, 2021 with a closest approach altitude of 1046 km. The trajectory approached Ganymede over its leading hemisphere or downstream from the moon relative to the co‐rotational flow of Jupiter's magnetospheric plasma. The trajectory projected into the z‐x and y‐x planes is shown in Figure y‐direction while the search coil's sensitive axis is parallel to the spacecraft z axis (spin axis). The response of the electric antenna is given in Sampl et al.  giving densities of 5–6 cm−3 and after 17:05 near 22 kHz giving an electron density of 6.5 cm−3 with densities up to about 12 cm−3 somewhat later. Panels e and f of Figure fce.Figure fce overlaid in Figures Panels d–f in Figure 2 intensity relationship as Juno approaches Jupiter. Third, the direction‐of‐arrival of these emissions using the rotating dipole technique  is clearly electromagnetic in nature.Figure Near 16:57:30 the obliquely propagating band shows a distinct decrease in amplitude, shortly after the change in character of the electron density profile. This band recovers in intensity, somewhat, about a minute later. The decrease in amplitude of the obliquely propagating hiss accompanies the appearance of the more nearly parallel‐propagating hiss.S, either parallel or anti‐parallel to the magnetic field  Ganymede. Later in the interval, the orientation of B is favorable for such determinations. The whistler mode hiss observed primarily in Region 3 exhibits a component of the Poynting vector parallel to B, hence, toward Ganymede. This would imply that the electrons generating these waves are moving away from the moon, assuming first order cyclotron instability. An example of the phase analysis supporting this result is given in Figure S4 in Supporting Information When there is a substantial component of Jupiter's magnetic field parallel to the spacecraft x axis, the phase relation between the electric and magnetic signals from the dipole antenna and search coil can be used to determine a component of the wave's Poynting flux, 3−3/∼6 to ∼24 (average ∼15) cm−3 here . Here, the Waves instrument found broadband bursts of plasma waves including ESWs demarcating entry into an extended wake with continuing bursty emissions up to the magnetopause. Multiple ECH emissions are observed just inside the magnetopause evolving into just one or two bands near fuh. These bands were observed to just beyond a local peak in the density at closest approach before a much more disordered set of emissions at the fuh. Below fce whistler‐mode emissions are observed. These include both quasi‐parallel and obliquely propagating chorus as well as quasi‐parallel hiss. ESWs were also observed at the outbound magnetopause crossing. A narrowband radio emission observed near 50 kHz, before and after the flyby, is likely generated in Ganymede's magnetosphere via mode conversion from electrostatic waves at frequencies related to fpe.Juno executed a flyby  of Ganymede before its 34th perijove. The Juno Waves instrument measured plasma waves associated with Ganymede's magnetosphere, including whistler‐mode chorus and hiss, ECH bands including a band at Supporting Information S1Click here for additional data file.


Low birth weight (LBW) is associated with infant mortality and postpartum health complications. In previous studies, overall LBW has been found to be significantly associated with several sociodemographic factors, including ethnicity, maternal age, and family income. Few studies have evaluated the association between environmental risk factors and LBW rates. This study investigated the effect of pre-birth water, sanitation, and hygiene (WASH) and housing conditions on self-reported low birth weight.The Ethiopian Demographic and Health Survey, which covered all administrative regions of Ethiopia from January to June 2016, provided data for this study. STATA version 16 was used to analyze 12,125 participants across weighted samples. Multivariable multilevel mixed-effect logistic regression analysis was conducted to determine the effects of each factor on the outcome while accounting for data clustering. The adjusted odds ratios and corresponding 95% confidence intervals were used to determine the statistical significance of the independent variables.One thousand five hundred and seventeen newborns, or 12.59% [95% CI (10.2- 15.3)], had low birth weights. When other factors were taken into account, the following factors were significantly associated with low birth weight: not using small-scale water treatment technology before using water [AOR (95% CI) 1.36 (1.08–2.23)], burning solid fuels for energy [AOR (95% CI) 1.99 (1.60–2.21)], living in homes with natural wall coverings [AOR (95% CI) 1.81 (1.47–2.21)], using a shared latrine within a woman's housing complex or compound [AOR (95% CI) 1.63(1.06–2.25)], and living in peripheral, isolated regions [AOR (95% CI) 1.38 (1.06–2.21)].A little more than one out of every ten deliveries in Ethiopia was under normal (recommended) weight. This study shows that poor housing conditions and lack of household WASH infrastructure are independent predictors of poor birth outcomes among Ethiopian women, adding to the limited evidence that environmental factors within the domicile contribute to low birth weight. Interventions to address these issues may help lower the prevalence of LBW. According to the World Health Organization (WHO), low birth weight (LBW) is defined as a weight of < 2500 g at birth. LBW is also a major cause of death among children under the age of five . The lonIt is well established that socioeconomic, demographic, and genetic factors affect LBW. In previous studies, race, maternal age and health, and family socioeconomic status were individual-level variables associated with LBW incidence –7. It ha2, CO, and O3) and particulate matter (PM10 and PM2.5) , were born underweight in the five years before the survey.Utilizing solid fuels, having unimproved wall covering, and not using point-of-use water treatment were found to be strongly associated with LBW when considering household-level factors. As per community-level characteristics, LBW was found to be significantly associated with living in small peripheral states in the multilevel multivariable mixed effects logistic regression analysis. When other factors were taken into account, households that did not employ small-scale water treatment technology before using water had a 1.3 times higher likelihood of having babies who were underweight at birth [AOR (95% CI) 1.36 (1.08–2.23)].The likelihood of neonates having low birth weight was also significantly associated with families using solid fuels for energy [AOR (95% CI) 1.99 (1.60–2.21)]. Infants with low birth weight were 1.8 times more likely to be delivered in dwellings where the walls were coated with natural materials [AOR (95% CI) 1.81 1.47–2.21)]. Using a shared sanitary facility within a woman's domicile or compound was also associated with a greater risk of low birth weight [AOR (95% CI) 1.63(1.06–2.25)]. Compared to metro inhabitants, those who lived in small peripheral regions were 1.3 times more likely to give birth to neonates who were below normal weight [AOR (95% CI) 1.38 (1.06–2.21)] . Nine percent of the national variation observed in the empty model was explained by individual, household, and community-level variables (PCV = 9%). When compared to the empty model, individual-, household-, and community-only models, and then again to the entire model, the values of AIC, BIC, and Deviance all indicated a continuous decrease. This demonstrates that the final model developed during the analysis had acceptable goodness of fit Table .Table 8Rth in the world for LBW mortality, with an age-adjusted death rate of 9.52 per 100,000 people  of newborns were delivered with low birth weight. This implies that Ethiopia still struggles with preventable events that might be averted by integrating prenatal health with housing and WASH interventions.There is a growing body of evidence, supported by biological plausibility, which indicates that poor water quality affects fetal and neonatal outcomes in a variety of ways , 27. WatHousehold water treatment (HWT), also known as point-of-use water treatment, offers a technique to reduce risk levels by treating water that has been contaminated at the source and by domestic handling in communities without consistent access to safe drinking water . AlthougNinety-four percent of Ethiopian families use solid fuels like wood, kerosene, and charcoal for cooking or heating . TraditiAccording to earlier studies, exposure to home air pollution during pregnancy can endanger both the mother and the unborn child. Carbon monoxide, the primary component of incomplete combustion, reacts with hemoglobin to generate carboxyhemoglobin, resulting in a diminished ability to carry oxygen to tissues and the growing fetus . As a reHistorical data from the United States and Europe support the theory that housing modifications have an impact on feto-maternal outcomes , 34. RegIn the present study, infants with low birth weights were more likely to be born in homes covered in natural cover than in those with finished walls. Given the rapid development currently occurring in sub-Saharan Africa, a full understanding of the protective efficacy of housing modifications is required to calculate the potential reductions in fetal morbidity and death. As a result, the Ethiopian government will need to work with the private sector to encourage housing development by increasing access to and upgrading the quality of the available stock, while also making it simpler for people to access land and housing finance.Research has shown that public toilets are a vital component of building sustainable, open, and inclusive communities. However, human feces is a major source of transmission for many common diseases, as well as many vaginal and urinary infections, which makes it crucial to offer hygienic public toilets . Today’sFew studies have specifically examined the influence of shared toilets on adverse pregnancy outcomes. Those that did, report that using a shared toilet was more likely to result in low birth weight than using a private family restroom , 40. ThiPeople who lived in small peripheral regions were more likely to give birth to neonates who were below normal weight than metro residents. The Ethiopian government has recognized the small peripheral regions Afar, Somalia, Benishangul, and Gambella as developing regional states because of the high prevalence of poverty and social metrics that trail far below national averages . While vThis study reveals that a lack of household WASH infrastructure is a risk factor for poor birth outcomes in women in low-income countries, adding to the scant evidence about environmental causes of LBW. To the best of our knowledge, this study is the first to quantify the proportional contributions of the individual-, family-, and community-level environmental factors that impact birth weight in Ethiopia. Despite the aforementioned benefits, this study has some limitations. Because the data were cross-sectional, they were inadequate for determining causal correlations. The lack of temporal data is unlikely to introduce any bias; however, major changes in housing standards and WASH services are unlikely to occur over such short periods. Another potential limitation of this study is the lack of information on housing features other than the building materials used to construct floors, walls, and roofs in the survey data. There is no information available about a home's interiors, such as whether the eaves are open or whether any windows or doors have screens. Finally, a recall bias may be introduced when measuring historical events.The intricate interactions between access to water, sanitation, and hygiene as well as housing conditions and birth outcomes among Ethiopian women were examined in this study. The study also provides opportunities for further research and insights that may have policy- and program-related implications for environmental and child-health programs. Important risk factors for LBW include households without a private source of drinking water, living in small peripheral regions, using solid fuels as the main source of energy, and households in which women handle their sanitary needs in shared or public spaces. Because of the multiple pathways through which poor access to water, sanitation, and hygiene may negatively impact newborn health outcomes, it is necessary to integrate WASH and housing considerations to support efforts within the newborn and child healthcare program in Ethiopia and vice versa to leverage greater progress in reducing neonatal mortality and morbidity.


To explore whether season and temperature on oocyte retrieval day affect the cumulative live birth rate and time to live birth.This was a retrospective cohort study. A total of 14420 oocyte retrieval cycles from October 2015 to September 2019. According to the date of oocyte retrieval, the patients were divided into four groups (Spring(n=3634);Summer(n=4414); Autumn(n=3706); Winter(n=2666)). The primary outcome measures were cumulative live birth rate and time to live birth. The secondary outcome measures included the number of oocytes retrieved, number of 2PN, number of available embryos and number of high-quality embryos.The number of oocytes retrieved was similar among the groups. Other outcomes, including the number of 2PN (P=0.02), number of available embryos (p=0.04), and number of high-quality embryos (p<0.01) were different among the groups. The quality of embryos in summer was relatively poor. There were no differences between the four groups in terms of cumulative live birth rate (P=0.17) or time to live birth (P=0.08). After adjusting for confounding factors by binary logistic regression, temperature (P=0.80), season (P=0.47) and duration of sunshine(P=0.46) had no effect on cumulative live births. Only maternal age (P<0.01) and basal FSH (P<0.01) had an effect on cumulative live births. Cox regression analysis suggested no effect of season(P=0.18) and temperature(P=0.89) on time to live birth. Maternal age did have an effect on time to live birth (P<0.01).Although season has an effect on the embryo, there was no evidence that season or temperature affect the cumulative live birth rate or time to live birth. It is not necessary to select a specific season when preparing for IVF. Struthio camelus) have found that overheating adversely affects the number of oocytes females lay rather than gamete viability  and time to live birth.This was a retrospective cohort study conducted at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University. This study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (2022–199–01). The oocyte retrieval time of the included patients was from October 2015 to September 2019. Exclusion criteria were as follows: ① Intracytoplasmic sperm injection (ICSI) or preimplantation genetic testing (PGT) cycle; ② oocyte recipient cycle, oocyte donor cycle, and oocyte freezing recovery cycle; ③ had not obtained oocyte cycle; ④ any chromosome abnormality in either spouse; ⑤ cycle with incomplete data.According to the date of oocyte retrieval, the patients were divided into four groups . Because the meteorological season can better reflect actual climate change, we used the meteorological season as the basis for grouping: spring (March to May); summer (June to August); autumn (September to November), and winter (December to February). Embryo evaluation standards refer to the Istanbul consensus . EmbryosThe primary outcome measures were CLBR and time to live birth. CLBR: In one IVF cycle , the number of cycles of the first live birth  was used as the numerator, the entire number of oocyte retrieval cycles was used as the denominator, and the end-of-observation standard was to obtain at least one live birth or utilize all of the embryos in the ovulation induction . The obshttp://data.cma.cn/), China’s surface climate data daily value dataset (V3.0). This study extracted the daily average temperature and cumulative daylight duration. All data presented in this article were obtained from the electronic medical record database of The Reproductive Center, The Third Affiliated Hospital of Zhengzhou University.Zhengzhou’s climate data were obtained from the China Meteorological Administration Meteorological Data Center ; ② summer (June to August); ③ autumn (September to November); ④ and winter (December to February).The details of the baseline and cycle characteristics among the four groups are described in The number of oocytes retrieved was similar among the groups. Other outcomes, including the number of 2PN (P=0.02), number of available embryos (P=0.04), and number of high-quality embryos (P<0.01) differed among the groups. The quality of embryos in summer was relatively poor Table 2.There were no differences between the four groups in terms of CLBR (P=0.17) or time to live birth (P=0.08). After adjusting for confounding factors by binary logistic regression analysis, season (P=0.47) Table 3,This study explored the effects of temperature and season on the cumulative live birth rate and time to reach live birth. We found that the CLBR and the time to live birth had no relationship with the season or temperature on the oocyte retrieval day.The effects of season and temperature on human fertility have been studied for many years, but exploring the effects of natural pregnancy also often includes exploring cultural behaviors and sociodemographic factors , 25. WitRegarding the clinical pregnancy rate and live birth rate, most early studies concluded that season and temperature were not independent factors , 36, 37.To further examine the effects of season and temperature on the day of oocyte retrieval on assisted reproductive technology, we evaluated the CLBR and time to live birth. The cumulative pregnancy rate assessment included the overall treatment outcome of both fresh embryo transfer and subsequent frozen embryo transfer cycles, reflecting the chance of a live birth throughout the course of treatment, which is of greater significance to both the patient and the clinician. CLBR is a more comprehensive and accurate indicator for evaluating the efficacy and safety of treatment. The time to live birth could be used to further evaluate the effectiveness of assisted reproductive technology, and we therefore analyzed the influence of temperature and season on live birth time using Cox regression. The association between seasonal variation and IVF outcomes has not been elucidated. Existing studies have published conflicting reports. Our study also does not support the conclusion that season or temperature affect clinical outcomes. It has been hypothesized that the mechanism by which season may affect the outcome of IVF involves serum vitamin D levels, increased vitamin D synthesis, and increased blood vitamin D levels caused by exposure to more sunlight in summer, which may influence assisted reproductive technology(ART) outcome . EvidencAnother strength of the present study is that we selected the cumulative live birth rate and time to live birth as measures of ART outcomes, and we used Cox regression to analyze the time to live birth. Another advantage is that we could adjust for confounding factors such as maternal age, basal FSH level, infertility type, and duration of infertility. In addition, the amount of data in this study was relatively large and reliable.Of course, there are some limitations to our study. First, we did not consider sperm parameters such as semen concentration, sperm motility, or normal morphology. However, we only included IVF cycles and did not include ICSI cycles with worse semen quality or abnormal fertilization. In addition, we used meteorological data for the day of oocyte retrieval to analyze the outcome, which may also have had an impact on the outcome. And there is a certain difference between the indoor environment and the atmospheric environment. In the future, meteorological data from other time periods may need to be considered to evaluate the outcome, such as the average temperature during oocyte development. Another limitation of the present study is that we did not consider the impact of atmospheric pollutants on the outcome and the effect of temperature on the drug. Finally, this study was a single-center, retrospective analysis, and the results therefore may not be able to be extended to regions with different climatic conditions.Although season has an effect on embryos, there was no evidence in the present study that season and temperature affect the cumulative live birth rate and time to live birth. It is therefore not necessary to select a specific season when preparing for IVF. Future multicenter studies should be conducted to further explore this question.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Third Affiliated Hospital of Zhengzhou University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.MD and YG designed the study and selected the population to be included and excluded. ZW, XL, ML, XW and JZ performed the data extraction and analysis. YG and LL reviewed the data. MD and JZ drafted this article. All authors have approved the final version of the manuscript. All authors contributed to the article and approved the submitted version.