To establish the association between serial levels of inflammatory cytokines in cord blood and perinatal characteristics and bronchopulmonary dysplasia (BPD) in preterm infants.147 premature infants with gestational age ≤32 weeks who were born and hospitalized in the First Affiliated Hospital of Zhengzhou University between July 2019 and August 2021 were enrolled in this retrospective case–control study. Multiple microsphere flow immunofluorescence was used to detect seven cytokines in cord blood collected within 24 h of birth. Demographics, delivery characteristics, maternal factors, neonatal characteristics, and clinical outcomes were collected for the two groups. An unconditional logistic regression model was used in this study to assess the clinical variables.IL-6 cord blood levels at birth were significantly higher in the BPD group than in the non-BPD group, but the odds ratio (OR) was very small (OR = 1). No differences in other cytokine concentrations were observed between the two groups. Multivariable logistic regression analysis demonstrated that increased maternal white blood cell (WBC) count on admission and lower birth weight increased the risk of BPD progression.Increased IL-6 cord blood levels at birth in preterm infants may have trivial significance for predicting BPD. Furthermore, higher maternal WBC count on admission and lower birth weight increased the risk of BPD. In 1967, Northway et al. first introduced the term bronchopulmonary dysplasia (BPD) to describe pulmonary injury in premature infants with respiratory distress syndrome (RDS) due to oxygen therapy and mechanical ventilation that showed imaging evidence of chest abnormalities at 36 weeks post-menstrual age . BPD conSeveral studies have shown that perinatal, neonatal, and postpartum factors are related to the onset of BPD, and little is known about antenatal factors. Our research has shown that a high maternal white blood cell (WBC) count on admission increases the risk of BPD, which suggests that perinatal factors related to systemic inflammation predispose patients to the development of BPD. Many factors, including preterm birth, exposure to supplemental oxygen, mechanical ventilation, proinflammatory mediators with inflammation, perinatal infection, inherited genetic factors, and postnatal infection, are involved in the progression of BPD . Among tAccordingly, this study aims to analyze the value of cytokine concentrations from cord blood samples obtained within 24 h of birth as a non-invasive biomarker and to determine clinical variables for identifying independent risk factors for the occurrence of subsequent BPD in premature infants.We performed a retrospective case–control study that was approved by the ethics committee of the First Affiliated Hospital of Zhengzhou University and for which informed parental consent was provided by all participants. The inclusion criteria were as follows: (1) a gestational age at birth below 32 weeks, (2) admission immediately after birth to our neonatal intensive care unit from July 2019 to August 2021 and survival until discharge, and (3) detection of cytokines within the first day of birth. The exclusion criteria were as follows: (1) major congenital malformations , (2) incomplete data, and (3) death before discharge. Among 147 preterm infants with a gestational age of ≤ 32 weeks that were hospitalized in our institution during the study period, 60 developed BPD, corresponding to an incidence of 40.8%.Clinical data on demographics, delivery characteristics, and maternal and neonatal factors were retrospectively obtained from the hospital's electronic medical record system. The demographic and delivery characteristics included gestational age (GA), birth weight (BW), small for gestational age (SGA), sex, mode of delivery, placental abnormalities , meconium-stained amniotic fluid, and 1- and 5-min Apgar scores. Data on maternal characteristics were also collected, including maternal age, multiple pregnancies, gestational hypertension, gestational diabetes mellitus (GDM), antenatal steroid administration, tocolytic treatment , premature rupture of membranes (PROM), intrauterine growth restriction, embryo transfer, and maternal WBC count on admission. Neonatal characteristics and the presence of neonatal morbidities, including continuous positive airway pressure, mechanical ventilation, surfactant therapy, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA), and sepsis, were obtained and recorded.BPD was defined as a requirement for >21% supplemental oxygen at 28 postnatal days, which was consistent with the standards of the National Institutes of Health . RDS andAn early blood sample from the umbilical cord was collected within the first 24 h of life, and the concentrations of cytokines  in the cord blood were detected by multiple microsphere flow immunofluorescence . The cytokine detection reagent was provided by Qingdao Raisecare Biotechnology Co, Ltd., Qingdao, China (Lot Number: 2019801) according to the manufacturer's recommendations. The normal ranges of IL-4, IL-6, IL-10, IL-12p70, IL-17, and TNF-α were 0–8.56, 0–5.4, 0–12.9, 0–3.4, 0–21.4, 0–16.5, and 0–23.1 (pg/ml), respectively.2-test and reported as frequencies (n) and percentages (%). The data were analyzed using IBM SPSS Statistics v. 25 software. All analyses were performed using 2-sided tests, and p < 0.05 was regarded as statistically significant.Unconditional logistic regression analysis was used to analyze clinical parameters significantly correlated to the onset of BPD. Quantitative data were obtained by performing a normality test (the Shapiro–Wilk test), and continuous variables were represented as by the mean ± SD if normally distributed and by medians and interquartile ranges otherwise. Qualitative data were analyzed by the χA total of 147 premature infants with gestational ages below 32 weeks were enrolled in our study, including 60 infants in a BPD group and 87 infants in a non-BPD group.p = 0.004] of the BPD group was lower than that of infants without BPD. There were no significant differences in other clinical variables, including gestational age (GA), small for gestational age (SGA), sex, delivery mode, placental abnormalities, meconium-stained amniotic fluid, and 1- and 5-min Apgar scores.Based on demographic and delivery characteristics , the bir9/L vs. 10.23 × 109/L; odds ratio (OR), 1.121; p = 0.02]. The difference remained insignificant in maternal age, multiple pregnancies, gestational hypertension, GDM, antenatal steroid administration, tocolytic treatment, PROM, intrauterine growth restriction, and embryo transfer rates between the two groups.The maternal perinatal data and clinical variables were comparable in both groups of infants as assessed by univariate analysis . MothersInsignificant differences in both groups of infants in terms of neonatal characteristics and clinical outcomes could be detected, including main clinical therapeutic strategies, such as continuous positive airway pressure, mechanical ventilation, and surfactant therapy, as well as major clinical outcomes, including RDS, IVH, PDA, and sepsis .p = 0.02) in the BPD group than in infants without BPD, but the OR was very small, and for every 1-pg/ml increase in the cord blood IL-6, there was a relatively small risk increase in the development of BPD . An insignificant difference was observed from cord blood samples in terms of other inflammatory cytokine concentrations  between the BPD and non-BPD groups  and low birth weight  were significantly associated with the development of BPD . This may be related to the late occurrence of BPD and the small gestational age of the cases we enrolled in the statistical analysis. In other words, the time span between the detection of umbilical cord blood IL-6 level within 24 h after birth and the occurrence of BPD is large, resulting in a smaller OR. In conclusion, to some extent, this suggests that cord blood IL-6 levels within 24 h after birth are associated with BPD.This research demonstrated that maternal factors related to perinatal inflammation, such as an elevated maternal WBC count on admission, were correlated with BPD and have not been mentioned in previous literature, which suggest that the occurrence of BPD is associated with antenatal intrauterine inflammation to some extent. It is well known that an elevated WBC count indicates maternal infection. Maternal infections may have an impact on the state of neonates. Premature neonates are particularly vulnerable to infections because of immature immune defense systems, incompletely developed skin barriers, and frequent requirements for invasive operations . Fetal eThe pathogenesis of BPD is multifactorial. However, a continuous inflammatory response may be a major contributor to the development of chronic lung disease . CytokinIn previous studies, the IL-6 level in cord blood samples obtained at birth has been used as a predictor of the occurrence and progression of BPD in premature infants, and elevated IL-6 levels have been reported to suggest intrauterine infection . The ratFurthermore, cord blood samples can potentially be used as a non-invasive biological marker to predict the risk of major neonatal outcomes, including retinopathy of prematurity , RDS 4141, necroIn this study, low birth weight was implicated as an important factor for BPD. This result was in agreement with those of several studies . This reThis study has some potential limitations. First, the case–control design made it difficult to avoid selection bias and recall bias in the enrolled study population. Second, the relatively small sample led to low statistical efficiency of the research results, such that the reliability of the conclusion needs to be confirmed. Therefore, we cannot rule out the occasionality of a significant difference in cord blood interleukin 6 levels between the two groups of infants. Further studies on large samples are also needed to investigate an association between cord blood cytokine concentrations and the progression of BPD in premature infants. Limited by its retrospective nature, most of the data  used in this study were collected from an electronic medical record system before enrollment of subjects. Therefore, all the clinical indices were accurately recorded, and maternal pregnancy outcomes were assessed during data collection. The present study had several strengths. First, the researchers who collected samples, recorded clinical indexes, and measured cytokine levels were blind to each other, which reduced the possibility of selection bias. Second, as foreign populations were investigated in previous studies, the Chinese population investigated in our study fills a gap in this field.Our study demonstrates that inflammatory cytokine levels in cord blood obtained on the 1st day after birth may have limited predictive ability for the development of BPD. In addition, maternal characteristics associated with perinatal inflammation, such as elevated maternal WBC count on admission, have been found to be correlated with the onset of BPD. Therefore, further research on a larger number of enrolled infants is needed to investigate a potential association between measured concentrations of multiple cytokines in blood samples of premature infants and BPD. The role of interleukins as pulmonary biomarkers in the development of BPD and even timely therapeutic interventions during pregnancy also need to be investigated in the future.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.QZ, MW, and CL designed the main purposes and methods of this study. MW wrote the article and QZ revised the article. ZS, XC, and ML participated in the index design and preliminary statistical analysis. WC, JZ, JG, MS, WD, YZ, and MZ participated in the data collection and critically reviewed the contents of the article. All authors agree to submit the final article and agree to be responsible for all aspects of the work.All phases of this study were supported by Science and Technology Department of Henan Province Project, No. 172102410017 (to QZ); Provincial and Ministerial Co-construction Project, No. SBGJ2018040 (to QZ); National Health Commission Medical and Health Science and Technology Development Center, No. VA2020HK41 (to QZ); Overseas Research and Training Project of Health Science and Technology Talents of Henan Province, No. HWYX2019066 (to QZ); Science and Technology Research Project of Henan Education Department, No. 20B320038 (to CL); and Joint Construction Project of Medical Science and Technology Public Relations in Henan Province, No. LHGJ20190064 (to ML).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


With the current global epidemic of obesity, especially among men, there is a need to understand its impact on adverse pregnancy outcomes. This study aimed to assess whether paternal pre-pregnancy body mass index (BMI) was associated with preterm birth and low birth weight in offspring.Multinomial logistic regression model was used to analyze associations between paternal BMI and preterm birth and low birth weight in different subgroups, the final model was adjusted for confounding factors of mothers and fathers. Further subgroup analysis was conducted to explore the stability of the risk associations.A total of 34,104 participants were included in this study, including 1,442 (4.2%) underweight, 13,930 (40.9%) overweight and 5,008 (14.7%) obese according to paternal BMI. The total incidence of preterm birth was 11.85% (4041/34104), and the incidence of low birth weight was 8.86% (3020/34104). In the total study population, compared with normal weight men, paternal pre-pregnancy overweight or obese was associated with a significantly increased risk of preterm birth  and low birth weight  in offspring. The results of subgroup analysis showed that the direction of the risk association was consistent, indicating good stability.Paternal pre-pregnancy overweight and obesity were associated with an increased risk of preterm birth and low birth weight in their offspring. In recent years, overweight and obesity have increased rapidly worldwide. Almost a third of the world’s population is now classified as overweight or obese . It is ePreterm birth and low birth weight are significant global health problems . It was Currently, most studies only focus on the impact of maternal body mass index (BMI) on pregnancy outcomes. Studies have found that overweight and obesity in women may be associated with an increased risk of pregnancy complications and outcomes, such as preterm birth, stillbirth, gestational diabetes, gestational hypertension and birth defects –18. HoweThe uncertainty of research evidence has brought obstacles to disease (preterm birth and low birth weight) prevention. It is well known that paternal pre-pregnancy overweight or obesity is a potentially modifiable and preventable factor for adverse neonatal outcomes. Therefore, we intend to explore the association between the paternal pre-pregnancy BMI and the preterm birth and low birth weight of the offspring through a prospective epidemiological investigation, so as to provide a scientific basis for reducing the incidence of diseases.The study was a prospective cohort study. The participants were couples who received their first antenatal care in the reproductive center, obstetrics department, infertility clinic, other departments of Hunan Maternal and Child Health Hospital from 13 March 2013 to 31 December 2019, and planned to continue the antenatal care and delivery in the same hospital. This study was approved by the Ethics Committee of Xiangya School of Public Health, Central South University, and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800016635). All participants provided written informed consent prior to participating in our study. This study complied with the ethical principles of the Helsinki Declaration of the World Medical Association.n = 9,944). For the purpose of this study, we excluded pregnant women with twins or above  (n = 661), with termination of pregnancy due to miscarriage, stillbirth and induced labor (n = 603), still pregnant at the end of follow-up  or lost to follow-up (n = 831), as well as men with implausible measurements of height (<150 cm) (n = 56) or weight (<30 kg) (n = 89) were excluded. A total of 34,104 subjects were included in the final analysis  may lead to overestimation of the prevalence of preterm birth and low birth weight, and there may be bias in estimating the impact of relevant risk factors. Therefore, the population using ART was not included in the analysis , and t-test was used for comparison; categorical variables were described by percentage and compared by χ2 test or Fisher’s exact probability method. The associations between paternal pre-pregnancy BMI and preterm birth and low birth weight were analyzed using a binary Logistic regression model. Then we further divided preterm birth into four groups according to gestational age and low birth weight into two groups according to birth weight. Multinomial logistic regression model was used to further analyze the association between paternal pre-pregnancy BMI and preterm birth and low birth weight. Odds ratio (OR) and 95% confidence intervals (CIs) were used to describe and compare the associations between different levels of factors. In above analysis, Model 1 was crude OR. Model 2 was adjusted for paternal age, maternal age, maternal BMI, residence location, education level, nationality, history of smoking, drinking, betel nut consumption, drug use, and per capita monthly household income .This study was reported following the STROBE statement . In the p < 0.05 was considered statistically significant.To assess the stability of the results, we analyzed the interactions effect between paternal age, residence location, and ethnicity and paternal pre-pregnancy BMI. Subgroup analysis was further performed by paternal age, residence location, and ethnicity. Using full-term birth and normal birth weight as reference, a binary Logistic regression model was used to estimate the risk associated with paternal BMI and outcomes (preterm birth and low birth weight) for each subgroup after adjusting for other covariables except subgroup variables. In this study, EpiData version 3.1  was used to establish the database by double entry to ensure the accuracy of the data. The data were statistically analyzed from 8 January 2022 to 20 January 2022 and the results were obtained. SPSS 26.0 software was used to analyze the data, and R 4.0.3 was used to draw the forest map. Two-sided In this study, 13,724 (40.2%) people were classified as normal weight, 1,442 (4.2%) were underweight, 13,930 (40.9%) were overweight, and 5,008 (14.7%) were obese according to paternal pre-pregnancy BMI. The mean age of the study population was 31.0 ± 4.8 years. Characteristics of study population classified by BMI were shown in In the total study population, the total preterm birth rate and total low birth weight rate were 11.85%  and 8.86% , respectively. We categorized preterm birth into four groups  and low birth weight into two groups . The incidence of preterm birth and low birth weight and their subtypes among the offspring in this study were shown in In the overall study population, we found that the paternal pre-pregnancy overweight  or obesity  was associated with an increased risk of preterm birth after adjusting for potential confounding factors. When preterm birth was divided into four subgroups according to gestational age, each group showed that paternal overweight was associated with a significantly increased risk of preterm birth in their offspring. Among them, the risk of extremely preterm birth was the highest . Apparently, it was also found that paternal pre-pregnancy obesity was associated with an increased risk of preterm birth in each group  .When analyzing the association between paternal pre-pregnancy BMI and low birth weight in the offspring, it was found that paternal overweight  or obesity  was associated with an increased incidence of low birth weight in offspring in the overall study population after adjusting for potential confounding factors. In contrast, paternal pre-pregnancy underweight may be a protective factor for low birth weight in offspring . A similar association pattern was observed when low birth weight was divided into two subgroups based on birth weight. Paternal overweight or obesity was also associated with low birth weight in offspring in both subgroups. However, it was not found that paternal pre-pregnancy underweight was associated with very low birth weight infants .p for interaction <0.001). Then we conducted a subgroup analysis of the association between paternal pre-pregnancy BMI and preterm birth and low birth weight. In the three subgroups, paternal pre-pregnancy overweight or obesity at all levels were associated with an increased risk of preterm birth and low birth weight in the offspring  after adjusting for the confounding effects of other covariables other than the subgroup factors. For rural area and minority nationality participants, the risk association was not found to be statistically significant, which may be related to small exposure, and the small sample size of each group in the subgroup analysis . Overall, the relationship between paternal overweight or obesity and preterm birth and low birth weight remained in the same direction, suggesting a stable risk association. In addition, we found that the risk of preterm birth and low birth weight was higher in the offspring of fathers with overweight or obesity in age ≥35 years than in the offspring of fathers with overweight or obesity in age <35 years. Moreover, the risk of preterm birth of fathers with obesity  in minority was higher than that of fathers with obesity  in the Han nationality  and low birth weight into two groups , these associations still existed. Subgroup analysis  also showed that the risk associations were stable. Therefore, our study suggested that paternal pre-pregnancy overweight and obesity may be risk factors for preterm birth and low birth weight in offspring.2) was associated with a low risk of low birth weight, preterm birth and SGA  in relation to the risk of preterm birth and low birth weight. We further performed subgroup analyses and found that the risk of preterm birth and low birth weight was higher in the offspring of fathers with overweight or obesity in age ≥35 years than the offspring of fathers with overweight or obesity in age <35 years. It may reveal that paternal age was also a risk factor for preterm birth and low birth weight in the offspring, which was similar to most of the studies . The patients/participants provided their written informed consent to participate in this study.MS conceptualized the study and drafted the initial manuscript. MS, SZ, and LC analyzed and explained the data. JD, SZ, JL, YHL, LC, YPL, JW, XS, and JS have collected the data. TW, PZ, and JQ conceptualized and designed the study and critically reviewed and revised the manuscript. All authors contributed to the article and approved the final version of the manuscript.


Discordant birth weight in twins is linked to poor outcomes and predicting this discrepancy may lead to enhanced screening and surveillance. Our purpose was to quantify the relationship between intertwin nuchal translucency (NT) and crown-rump length (CRL) discordance with birth weight discrepancies ≥ 20%. T-test were performed as appropriate. We then used published data and receiver operating curves to determine the optimal thresholds for predicting birth weight discordance based on first trimester intertwin NT differences. These values were used in multivariate logistic regression models accounting for known confounders.  We conducted a retrospective cohort study of 887 live twin births delivering at a Canadian tertiary care center over a 7-year period who opted for integrated prenatal screening. Categorical data are presented as numbers and percentages, and continuous data are expressed as means and standard deviations. Chi-square tests, Fisher's Exact tests, or th percentile, an NT difference ≥ 0.9 mm was predictive of birth weight discordance ≥ 20% .  Roughly 16% of twin pairs exhibited ≥ 20% difference in birth weight. Twin pairs with a CRL discordance greater than 10% have nearly a 4 times greater likelihood of having a birth weight discordance greater than 20%  while controlling for chorionicity, maternal age, gestational age at delivery, maternal body mass index (BMI), and parity. In these models, intertwin NT discordance ≥ 20%  and NT discordance ≥ 14%  were not statistically significant predictors of twin birth weight differences. However, when evaluating the effect of the larger intertwin NT value corresponding to the 95 Although intertwin CRL and NT discordance measured via ultrasound between 11-14 weeks gestation are related to birth weight discordance, there is uncertainty as to whether twin birth weight differences are related to adverse pregnancy outcomes in this population. The incidence of twin pregnancy has increased over the past several decades due to delayed childbearing and increased use of new reproductive technologies . CurrentDuring the first trimester differences between cotwins in fetal measurements made on ultrasound examination are suggested to be early markers of twin complications including discordant fetal growth . At presIn our region NT measurement, as part of early aneuploidy screening, is offered to all pregnant women as part of standard obstetrical care. As opposed to looking specifically at loss rates or adverse outcome data as has been reported previously –13, we aWe conducted a retrospective cohort study of all live twin births delivering over a 7-year period who opted for first trimester screening. To better understand the relationship between CRL and NT discordance and birth weight discrepancies > 20%, we collected data on 887 patients with monochorionic-monoamniotic (MCMA), MCDA, and dichorionic-diamniotic (DCDA) twin pregnancies from a tertiary care center in Canada. Data were extracted from the electronic medical and birth records of mothers and their twin offspring. Exclusion criteria included fetuses with documented chromosomal abnormalities, structural anomalies, intrauterine death of a cotwin, TTTS, delayed interval delivery of a second twin, and pregnancies of higher fetal order with a monochorionic twin. We included twins of all types of placentation  in our analysis. DCDA twins were included while they too may exhibit significant growth discordance although the clinical implications and sequelae of discordant growth in this twin group can differ from those of the MC population . We aimeth percentile was equal to 0.9 mm. CRL discordance (%) was calculated as 100 × /larger CRL. For purposes of our analysis, a CRL discordance of > 10% is considered clinically meaningful, based on previously published literature [Measurements of the CRL and NT were taken between 11‐13 weeks + 6 days gestation as determined by ultrasound. NT discordance (%) was calculated as 100 × /larger NT. An NT difference of > 20% was considered clinically meaningful and based on previously published literature , 11. Nexterature . The priterature  as it haterature , 6. BivaT-test was performed as appropriate. Further multivariable logistic regression was used to examine the effect of NT discordance on intertwin birth weight difference, adjusting for clinically relevant covariates including chorionicity, maternal age, gestational age, maternal pregravid body mass index (BMI), and parity. We reported odds ratio (OR) and 95% confidence intervals (CI). All analyses were conducted using SAS version 9.3 (SAS Institute Inc). All statistical tests were 2-sided. The study protocol was approved by the institutional research ethics board (study protocol number REB20140143-01H).We first compared baseline maternal characteristics and fetal outcomes in live twins by group (intertwin birth weight differences less than 20% vs. greater 20%). Categorical data are presented as numbers and percentages, whereas continuous data are expressed as means and standard deviations. Chi-square tests, Fisher's Exact tests, or In our retrospective study complete data was available for a total of 887 healthy, live twin pregnancies. Maternal characteristics at baseline, including age, BMI, IVF, fetal sex distribution, chorionicity, and parity, were not different between groups when categorized according to ≥20% birth weight discordance . Eighty Prior to multivariable modeling we performed a collinearity diagnostic test that showed no collinearity among variables in our models. A CRL discordance of > 10% is considered clinically meaningful  and was th percentile was equal to 0.9 mm, and this value was used in multivariable analysis. When the intertwin NT difference was greater than 0.9 mm, there was a 2.5 greater likelihood that birth weight discordance would be greater than 20% . Of note, the relationship between gestational age at delivery was also statistically significant  were associated with twin birth weight discrepancy. Furthermore, we show that CRL discordance greater than 10% and an absolute NT difference corresponding to the 95th percentile are associated with an increased likelihood of twin birth weight discordance greater than 20%.In this single-centered retrospective Canadian twin cohort, we evaluated the effect of first trimester intertwin NT and CRL differences measured via sonography on birth weight discordance given its reported relationship with neonatal morbidity and mortality. Using strict inclusion and exclusion criteria, we aimed to determine if abnormal growth in fetuses without anomalies or TTTS can be detected early in trimester one. In this highly selective healthy live-twin population, nearly 1 in 5 twin pairs exhibited ≥ 20% difference in birth weight. In line with our hypotheses, intertwin CRL difference greater than 10%, NT discordance (> 20% and > 14%), and absolute NT difference greater than 0.9 mm  of these twins had birth weight discordance ≥ 20%. When chorionicity was verified with pathology, we showed that in a total of 143 MCDA twin pairs, 23/143 (16%) of these had birth weight discordance ≥ 20%. The small discrepancy in assignment of chorionicity between methodologies may reflect, in part, different denominators in the groups. In some instances, chorionicity was established solely by pathological examination of the placenta (the gold standard), whereas others only were established by ultrasound if the placenta sample was not available for examination. Despite these findings, it is important to note that chorionicity was not significantly different between birth weight groups (< 20 vs. ≥ 20) in our study and was unrelated to the primary outcome of birth weight discordance in multivariate analysis.A limitation of our study is the retrospective nature of the analysis which precludes causal inferences from being made and the fact that the data came from a single tertiary care center which limits generalizability. The strengths of our study include a large sample size and single center nature of data collection and clinical care. All twins in our dataset with significant growth discordance were cared for by the same group high-risk specialists which increases the internal validity of the results. At our institution, we have strict quality assurance procedures in place with respect to credentialing sonographers and sonologists performing the thousands of NT measurements at our institution annually. Similarly, with respect to birth weight data, this variable is captured in a validated province-wide database. Thus, we can speculate that the interobserver variability among NT and birth weight measurement is low and unlikely to affect our outcome.th percentile) with twin birth weight discrepancy. Furthermore, we show that CRL discordance greater than 10% and an absolute NT difference corresponding to the 95th percentile are associated with an increased likelihood of twin birth weight discordance greater than 20%. Pregnancies with high CRL and NT discordance captured during the first trimester warrant careful surveillance to ensure healthy interval growth of each twin and patient counselling as per current guidelines.In summary, we found a positive association between first trimester intertwin CRL difference greater than 10%, NT discordance (>14%), and absolutes NT difference (greater than 95


The aim of this study was to examine birth outcomes in areas affected by Hurricane Michael.Vital statistics data of 2017–2019 were obtained from the state of Florida. Births occurring in the year before and after the date of Hurricane Michael  were used. Florida counties were divided into 3 categories reflecting extent of impact from Hurricane Michael. Birth outcomes including incidence of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) were also compared before and after Hurricane Michael. Spontaneous and indicated PTBs were distinguished based on previously published algorithms. Multiple regression was used to control for potential confounders.Both LBW  and SGA  were higher in the year after Michael than the year before in the most-affected area; a similar effect was not seen in other areas. A stronger effect was seen for exposure in the first trimester or in the 2 months after Michael than in the second or third trimester.Consistent with many previous studies, this study of Hurricane Michael found an effect on fetal growth. Effects on preterm birth (PTB)/gestational age have been found much less often.12 Studies that have addressed both birth weight and gestational age have tended to find stronger effects on birth weight, if they find an effect at all,28 and only a few have found an effect on PTB but not low birth weight .30Disasters have been associated with poor birth outcomes. Most consistent are modest effects on birth weight, generally examined by region of residence and timing of birth. Magnitude of effect has ranged from 160 g decrement in birth weight associated with the Wenchuan and Haiti earthquakes32; for instance, male fetuses are usually larger but are more likely to be born early, and smoking is a clear risk factor for LBW but is less strongly associated with PTB. If disaster has different effects on these outcomes, it may indicate mechanisms; for instance, effects limited to growth-related outcomes might suggest a focus on behavior, for example, nutrition and smoking.This is surprising as LBW and PTB co-occur, with early delivery being a common cause of LBW. Best practice is usually considered to analyze small for gestational age  rather than LBW per se, because birth weight is affected both by length of gestation and fetal growth. PTB and LBW have overlapping but not completely identical risk factors18; strongest effects in the first trimester34; strongest effects in the second trimester36; strongest effects in the third trimester25; as well as variation in strongest effects by exposure, outcome,5 and their combinations.8 Theoretically, effects in the first trimester may be more strongly related to placentation, while later effects are more likely to relate to growth or immediate labor triggers.A secondary issue is that of timing of exposure to disaster, where results have again been inconsistent for both birth weight and gestational age. Studies of disaster and related time-specific stressors such as terrorist attacks have found no difference by trimester of exposure37 Hurricane Michael hit a primarily rural, less populated area. This study analyzed the data for changes in birth outcomes to address 3 questions: (1) Was Hurricane Michael associated with changes in incidence of LBW and PTB? (2) Did the storm have differential associations depending on its timing in pregnancy?—and (3) Were there similar associations with LBW and PTB, and if not, can subtypes of these conditions be distinguished, perhaps to provide information on distinctions between the two?In examining effects of disaster on pregnant women, it may therefore be useful to compare and contrast effects on birth weight, weight for gestational age, and gestational age. Unlike other hurricanes where the focus has been effects on major cities,Vital statistics data of 2017–2019 were obtained from the state of Florida. Births occurring in the year before and after the date of Hurricane Michael  were used to assess changes in births and birth outcomes in counties affected by Hurricane Michael.38 Florida counties were divided into 3 categories reflecting extent of impact from Hurricane Michael: counties receiving both public and individual assistance (Area A), counties receiving only public assistance (Area B), and counties receiving neither public nor individual assistance (Area C).  The category of each county can be found in Based on FEMA disaster declarations,39The total number of births during October 6, 2017–October 6, 2018 and those during October 7, 2018–October 7, 2019 were compared. Birth outcomes including incidence of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) were also compared before and after Hurricane Michael. PTB was defined as a birth before 37 weeks of gestation. LBW was defined as a birth weight of an infant of 2500 g or less, regardless of gestational age. SGA was defined by birth weight below the 10th percentile for gestational age based on the national standard.40 Indicators of spontaneous births included premature rupture of membranes, labor characteristics, and vaginal birth, while induction and C-section were associated with indicated PTB . Using the Ohio birth certificates from 2006 to 2012, the kappa statistic of the algorithm was 0.68 ; predictive values for spontaneous and indicated onset were 85%  and 89% . While generally a good-quality algorithm, distinguishing spontaneous and indicated births can be difficult even in medical records, especially in cases of premature rupture of membranes.41We used the algorithm reported by Klebanoff et al. to distinguish spontaneous versus indicated preterm births.Births were categorized into 5 categories according to time relative to Hurricane Michael. Babies who were delivered before October 7, 2018 were categorized into category “before” Hurricane Michael. Women’s exposure was categorized by trimester on October 7, 2018: first trimester (< 14 weeks), second trimester (14 ≤ 28 weeks), and third trimester (28 weeks+), as well as pregnant within 2 months after Hurricane Michael in a “within 2 months after” category. The timing of 2 months was chosen because it allows those pregnancies to have more than 42 weeks  before October 6, 2019.42 The 4-level categorization is important as it helps distinguish complicated pregnancy  from those that receive limited or acceptable levels of care.Maternal age, race, education, and whether enrolled in the U.S. Department of Agriculture’s special supplemental nutrition program for women, infants, and children (WIC) program were considered as confounders because those variables are known risk factors for adverse birth outcomes and their distribution among women giving birth could have shifted after the hurricane. Access to antenatal care (ANC) services before and after Hurricane Michael was evaluated by whether pregnant women had any ANC visit before delivery, the month of the first ANC visit, and the Kotelchuck Index. There are 4 adequacy categories in the Kotelchuck Index: adequate plus, adequate, intermediate, and inadequate.Covariate missing data were minimal: maternal age (0.0025%), education (0.97%), race/ethnicity (1.28%), pre-pregnancy body mass index (BMI) (5.63%), whether enrolled in the WIC program (1.24%), smoking during pregnancy (0.38%), and alcohol drinking during pregnancy (1.51%)—so, a complete case analysis was used. Paired t-tests were used to compare the number of births before and after Hurricane Michael. Linear regression was used to assess whether the change in the number of births was different across different areas. Log-binomial regression was used for binary outcomes; if these failed to converge, logistic models were used. All of the estimates were compared unadjusted and after adjusting for potential confounders. Comparisons were made in 2 directions: before and after Hurricane Michael, and among different levels of exposure. In order to assess these factors jointly, an interaction term was also added in unadjusted and adjusted models. The analysis was also performed stratified by trimester of exposure. Statistical analyses were performed using the software SAS 9.4 .These analyses were conducted under a waiver of informed consent and approved by the Institutional Review Boards of Tulane University, Florida State University, and the Florida Department of Health.There was a total of 218 903 and 217 966 live births in Florida between October 6, 2017–October 6, 2018 and October 7, 2018– October 7, 2019, respectively. The total numbers of live births were not significantly different before and after Hurricane Michael within each affected area. The change in the number of births across categories of affected areas was not significantly different (P for interaction = 0.83).The racial composition, mean maternal age, pre-pregnancy BMI, and gestational age at birth were similar before and after Hurricane Michael within each affected area . The perP for interaction = 0.002). However, the effect was not different between areas B and C.There was a higher proportion of LBW among counties in area A after Michael, adjusting for age, education, ethnicity, pre-pregnancy BMI, and participation in WIC , but the proportion of LBW did not change after Michael among areas B and C . Mean deThere was a higher proportion of PTB within area B after Michael, adjusting for covariates , but the proportion of PTB did not change after Michael within area A or C . There wP for interaction = 0.01) but not in area B (P= 0.40).There was a higher proportion of SGA in area A after Michael, adjusting for covariates  see . CompareWithin the most affected area A, exposure during the first trimester  or pregnancy within 2 months after Michael  showed the highest increases compared to before the hurricane. These increases were not seen in the unaffected areas; the moderately affected area showed a small increase in risk among conceptions in the 2 months after the hurricane . CompariWithin the moderately affected area B, exposure during the first trimester  or pregnancy within 2 months after Michael  showed the highest increase in PTB compared to before the hurricane. These increases were not seen in the area A or C see . When coWithin the most affected area A, exposure within 2 months after Michael  showed increased risk for SGA compared to before the hurricane, which was not seen in the unaffected areas see . Women lArea B seemed to be at higher risk for induced PTB , regardl43 and with similar effect sizes.25 These effects appeared to be stronger among women who experienced the storm in the first trimester, or who conceived shortly after the hurricane, compared to those exposed in the second or third trimester. These findings are consistent with several studies showing the strongest effects with first-trimester exposure.34The impact of a hurricane on a less populated area on maternal and child health outcomes, specifically LBW, PTB, and SGA was examined. Vital statistics data from counties were categorized by degree of damage caused by Hurricane Michael. Overall, an increase in LBW and SGA was found in the most-affected areas, consistent with previous studies,45 and 1 recent analysis examined only spontaneous births, whether preterm or not,46 but that has not necessarily led to any more consistent results.Strengths include the large sample size and consideration of multiple definitions of exposure and outcome. Limitations of the study include the reliance on vital statistics, defining exposure by county-level damage and timing, and the lack of information on physiologic, behavioral, or social mechanisms of effect. Future analyses will explore some of these topics in more detail. While a validated classification system was used for spontaneous versus medically indicated preterm births, such systems are still limited relative to detailed research or medical record review. Further subtyping was not possible, and distinctions among preterm premature rupture of membranes (PPROM) and preterm labor or different indications for induction  might be relevant to understanding effects of a complex exposure like disaster. A few studies have examined effects of disaster on PPROM alone,47 while another found decreased odds of moderate PTB for several weeks post-disaster and increased odds of very LBW around 4 months later,14 but no effects on other outcomes or during other post-disaster time periods. A study of Hurricane Katrina suggested some effects lingered 5–7 years later,48 while 1 study of county-level PTB rates after disasters found effects lasting only for 2 to 3 weeks after the hurricane exposure.46 As many of the effects of disaster exposure—stress, economic problems, lack of access to health care—linger for months or years, it is reasonable that exposure to post-disaster life early in pregnancy would have similar effects.Few studies have considered the post-disaster period. One study of 9/11 found minimal difference in effects between women who were pregnant at the time of the attack and those who became pregnant later,28 especially confusing as there was an increase in the moderately exposed counties. This is somewhat surprising, as PTB and LBW often go hand-in-hand and some large and detailed studies have found an effect.46 Gestational age is often measured less precisely and consistently than birth weight, which may make effects more difficult to detect. For birth weight, where an effect was found, the absolute size of the change was small. Third-trimester effects must be examined carefully, as women who give birth preterm have a shorter third trimester, but this should not affect estimate of first-trimester effects. One analysis of the spatial hazards data across the United States concluded that disaster affected birth weight more strongly in counties that were less vulnerable, while gestational age was most affected in more vulnerable counties,8 and Sun et al. also concluded that effects on PTB are stronger in areas with high social vulnerability.46 Based on the Centers for Disease Control and Prevention social vulnerability index,49 the counties in the affected areas were either ranked highly  or moderate to highly vulnerable . However, a stronger effect was found on birth weight compared to PTB. It is possible that a hurricane could have specific effects, triggering preterm labor alone, for instance, or lead to complications such as hypertensive disorders that would be mainly apparent in induced PTB, but examination of spontaneous versus induced PTB failed to reveal any patterns.Also consistent with previous studies is the lack of effect on PTB in the most-exposed counties,11 the overall number of births in the affected areas did not change significantly; therefore, selective fertility or migration is unlikely to be a cause of the findings.50There are several possible mechanisms by which disaster could affect birth weight, including health behaviors such as increased smoking and an unhealthy diet, reduced fetal growth due to higher stress hormones and blood pressure, and increased susceptibility to infection. Our models controlled for covariates that appeared to change between time periods, but the possibility for residual confounding remains . Unlike Hurricane Katrina,The decreased enrollment in WIC also suggests possible nutritional effects. Although enrollment is theoretically possible during and after disaster, there are several possible reasons for this decline: physical and communication barriers; evacuation separating women from normal care; the general mental toll of rebuilding , which may limit the time and energy available to sign up. Facility shutdowns are another consideration. In some of the affected counties, such as Leon, there was no interruption to services, and benefits were uploaded to recipients’ accounts so they did not need to come into the office. In others, such as Bay County, health departments and offices were shut down for some weeks.51 or means,8 time series,14 sibling studies,4 and treating the hurricane as a time-varying exposures in a proportional hazards model.52 Difference-in-difference analysis assumes confounders are time-invariant, which may not be realistic, as disaster may induce differential shifts in covariates such as ethnic distribution.51 Studies also vary in whether the control group is other unaffected areas or the same area, cohort, or clinical population in a previous or later time period; both types of comparisons were performed. Studies with very fine time scales52 or that allow only for exposure in late pregnancy52 inherently focus on hurricane exposure as a short-term trigger. Given the long-term effects of disaster on so many aspects of life, this seems to represent a limited window.Our analytical strategy, which is at the individual level and examines maternal residence at the time of the hurricane, is probably the type most frequently used in the literature and allows for control of individual-level confounding. Defining exposure by place of delivery might provide additional information on effects on the health care system, but maternal residence provides a better estimate of individual overall hurricane exposure. Other analysis strategies have been used, such as comparisons of county-level rates53 PTB so rarely rises in the aftermath of a major stressor. Some argue for PTB as an adaptive response under some conditions; the inverse—adaptive extension of gestation under conditions of stress—could also be hypothesized.54 It may be that disaster-associated stress contributes to PTB more in the context of chronic or social determinant of health-associated stress, rather than as a short-term stressor. Further studies employing more detailed phenotyping and measurement of mediating factors may be necessary to more comprehensively ascertain these disaster-related effects on maternal and child health (MCH). However, given the large amount of research on the topic, it may be time to move to developing interventions to improve post-disaster outcomes.This study adds to the body of evidence, suggesting an effect of disaster on pregnancy outcomes, particularly fetal growth, and that effects early in pregnancy may be particularly severe. The lack of effect on preterm birth is also consistent with many previous studies and warrants further study as to why, if stress is a cause of PTB,1


Economic precariousness has taken on a central role in explanations of the postponement of childbearing in developed societies. However, most studies conceptualize and operationalize precariousness as being static and one-dimensional, which provides only a partial perspective on the links between precariousness and fertility. In this paper, we study precariousness as a dynamic and multidimensional concept, distinguishing between past and current precariousness as well as between precariousness relating to income and to employment. Analyses are based on Dutch full-population register data. We select all inhabitants of the Netherlands who left education in 2006 and follow them until 2018. Event history analyses show that current and past income and employment precariousness all have independent negative effects on the first birth rate for men. Current and past employment precariousness and past income precariousness also reduce the first birth rate for women, but current income precariousness increases women’s probability of first conception. When precariousness is both persistent and multidimensional, it is associated with a threefold decrease in the monthly probability of conceiving a first child for men and almost a halving of the probability for women. Our analyses show the need for going beyond static and one-dimensional analyses in order to understand how economic precariousness may affect fertility behaviour.The online version contains supplementary material available at 10.1007/s10680-022-09617-4. The notion of economic precariousness has taken on a central role in explanations of the postponement of childbearing in developed societies. As ongoing changes on the labour market have made the employment position of young adults increasingly precarious employment or (a low) income. One may, however, assume that income-related and employment-related precariousness have separate accumulating effects on fertility decisions, which makes it important to study these two dimensions together. This is in line with recent studies on labour market dynamics, which stress the dynamic and multidimensional nature of employment careers  frequently attributed to the precarious economic situation of young adults  current income and employment precariousness decrease first birth rates.Most recent studies expect that the experience of current economic precariousness makes both men and women postpone the transition to parenthood  past income and employment precariousness decrease first birth rates over and above the effect of current precariousness. Again, this may be a result of a direct effect of past precariousness on childbearing decisions as well as an indirect effect that runs through lower levels of union formation and union stability.Most previous studies on the relationship between economic precariousness and fertility have focused on the current experience of precariousness, based on the assumption that the current experience will figure prominently in evaluations of the suitability of one’s economic position for raising a child and will have a direct impact on expectations about the future. This has been criticized by some recent studies, however, which argue that a focus on the current economic position provides an incomplete picture of the influence of precariousness on fertility behaviour  first birth rates are lowest among persons who experience persistent precariousness. On the other hand, individuals who face persistent precariousness may realize that they are unlikely to ever fulfil the normative requirement of parenthood in the form of a stable job and income, and therefore disconnect their childbearing desires from economic conditions  first birth rates are higher among persons who experience persistent precariousness than among persons who experienced precariousness only in the past or only in the current situation.As economic precariousness tends to cluster in time, some individuals will experience precariousness both in the past and in the present  first birth rates are higher among persons who recently made a transition out of precariousness than among persons who did not experience precariousness at all. Some evidence for the relevance of such transitions out of precariousness is provided by Barbieri et al. ((H4b) first birth rates are higher among persons who recently made a transition into precariousness than among persons who did not experience precariousness at all. Schmitt’s , a system of interlinked registers containing information on the full population of the Netherlands. The SSD combines information from a wide range of administrative registers (e.g. tax and school registers), which are linkable by unique identifiers for individuals, households, buildings, and organizations  over the entire observation period are evaluated in an additional analysis, in which the measurement of past precariousness is confined to months in the more recent past.Current employment precariousness is measured by a person’s main activity in the current month. We distinguish between permanent employment , temporary employment , self-employment, and different types of joblessness. Although based on the register data we are not able to distinguish between unemployment and inactivity as is often done (i.e. where persons are coded as unemployed only if they are actively searching for employment), we can differentiate different types of joblessness based on the type of benefits persons receive. A first category includes persons who receive unemployment benefits. Eligibility for receiving these benefits is based on previous employment experience. As a result, those who receive unemployment benefits have necessarily been employed in the recent past and can arguably be seen as the least precarious of all jobless persons. In contrast, social assistance benefits (bijstandsuitkering in Dutch) are not tied to previous employment, but are available to persons who can demonstrate that they are unable to make ends meet based on their own income and financial capital. We further distinguish a category of persons who receive illness, disability, or other benefits, referring to those who are unable to work due to disability or sickness. A last category comprises people who are jobless but do not receive any benefits. This includes a diverse group of people, ranging from persons who are looking for work but not eligible or willing to apply for benefits to persons who are voluntarily jobless.4Past employment precariousness is measured using a continuous variable for each of the main activity categories, which indicate the proportion of months that a person spent in that activity between the start of the observation period and the current month, excluding the current month. These variables range from 0 (no months in the past were spent in that activity) to 1 . As stated above, additional analyses explore how the effect of past employment precariousness changes when its measurement is limited to the more recent past.trajectories of income precariousness, current precariousness is indicated by an income in the current month that is below 1500 euros (in January 2006 euros), whereas past precariousness is defined as having earned an average monthly income between the start of the observation period and the current month that was below 1500 euros. For trajectories of employment precariousness, the current situation is defined as precarious if a person is jobless, and the past is defined as precarious when a person was jobless for more than 20% of the months between the start of the observation period and the current month. We also use these definitions of current and past income and employment precariousness to create a variable that counts how many types of precariousness are experienced. This variable ranges from 0  to 4  and allows us to examine the total effect of the accumulation of precariousness on the first birth rate. All variables that measure precariousness (including those measuring the trajectories of precariousness and the accumulation of precariousness) are measured using time-varying variables, and as such their values change as persons’ income and employment careers unfold.To measure precariousness trajectories, we create categorical variables that indicate whether persons were (1) not in a precarious situation in the past nor in the current month ; (2) experienced precariousness only in the past (transition out of precariousness); (3) experienced precariousness only in the current month (transition into precariousness); or (4) experienced precariousness in the past as well as the current month (persistent precariousness). For This combination of measures of economic precariousness provides a good overview of the experience of past and current income and employment precariousness by persons in our study population as measured by objective characteristics. At the same time, the register data do not contain subjective information on economic experiences, making it impossible for us to distinguish between the effects of decreased financial resources, increased uncertainty, and increased stress.All models control for educational level, indicated by the highest level of completed education and measured on a yearly basis. We categorize this variable based on the International Standard Classification of Education (ISCED). The level of education is unknown for 4.1% of all person-months because it was not observed in the registers (e.g. because of education at a private institution or abroad). These person-months are assigned to a separate category termed ‘unknown’. The largest educational group (ISCED 3: higher secondary education) is chosen as the reference category. In addition, a time-constant variable is included that indicates a person’s ethnicity, based on his/her country of birth and the country of birth of his/her parents. Finally, age and duration since the start of the observation period are included as control variables, using both a linear and a quadratic term for age minus 15 as well as a linear and a quadratic term for the number of months since the start of the observation period. An interaction effect between educational attainment and age (including its squared term) is also included in all models to account for the strong variation in the age at first birth by educational attainment . On average, 0.47% of men and 0.76% of women in our data conceive a first child each month. At the end of the observation period, 49.77% of men and 66.84% of women have conceived a first child.Table Results of the models including current (Model 1) and past Model 2) income and employment precariousness are shown in Table  income aAdding past precariousness in Model 2 shows that having earned an average monthly income in the past that was below 1500 euros lowers men’s first birth rates, even after taking into account the current income. Again, men’s likelihood to become fathers increases roughly linearly with income when past income exceeds 1500 euros a month. For example, having earned an average monthly income in the past that was below 1000 euros decreases men’s probability to conceive a child by almost a third compared to men whose past income was between 2000 and 2500 euros (the average monthly probability decreases from 0.50 to 0.34%). In addition, the variables measuring past employment precariousness show that a larger proportion of months spent in temporary employment and joblessness in the past is associated with a reduced first birth rate, after taking into account the effects of the current position. Whereas past temporary employment only has a small negative effect on the first birth rate, past experiences of all four types of joblessness strongly decrease the likelihood to become a father. These results confirm the hypothesis (H2) that past precariousness decreases first birth rates over and above the effect of current precariousness. In fact, past precariousness has a negative effect on first birth rates that is roughly similar in size to the effect of current precariousness, and model fit strongly improves after adding past precariousness to the model. Moreover, even though the negative effects of men’s current precariousness decrease once past precariousness is included in Model 2, current precariousness continues to decrease the first birth rate in most cases, showing that men’s experiences of current and past precariousness have independent negative effect on the transition to fatherhood.Turning to the results for women, women’s current employment precariousness is found to have a strong negative effect on the first birth rate that is similar to that for men. Women in permanent employment have the highest likelihood to become mothers, followed by women who are self-employed and women who are working on a temporary contract. First birth rates are lowest for jobless women, particularly for those who receive social assistance benefits or illness, disability, or other benefits. In contrast, women’s current income generally has only small effects on the first birth rate, and contrary to what was expected women who earn less than 1000 euros in the current month are more likely to become mothers than women with a higher income. In sum, for women the hypothesis (H1) that current precariousness decreases the first birth rate is confirmed for employment precariousness but not for income precariousness.The results of Model 2 show that women’s past income precariousness does have a strong negative effect on the first birth rate. Further, the effect of women’s current income precariousness becomes more clearly positive in Model 2. Thus, having earned a low income in the past decreases women’s first birth rate, whereas after taking into account the effect of past income precariousness women who currently earn a low income have a higher rate of becoming mothers. Women who experienced more months in the past in which they received unemployment benefits, received illness, disability or other benefits, or were jobless but did not receive any benefits also have a decreased likelihood of becoming mothers. For example, women who were jobless but did not receive any benefits in half of all months in the past are about one fifth less likely to conceive a first child than women who did not experience joblessness without benefits in the past (the average monthly probability to conceive a child decreases from 0.77 to 0.61%). In contrast, past temporary employment and past social assistance benefits have no effect on women’s first birth rate. To conclude, although there are some exceptions, the results for women generally also confirm the hypothesis (H2) that the experience of past precariousness lowers the first birth rate even after taking into account the effects of current precariousness. This is further supported by the finding that model fit substantially improves after including past precariousness in the model.Model 3 Table  shows thThe effects of women’s employment trajectories reveal that women’s employment precariousness has a particularly strong negative effect on the first birth rate when it is persistent, i.e. when it is experienced in the present as well as the past, again supporting hypothesis H3a but not H3b . The results of these additional models show that taking into account the entire observation period—as was done above—provides the best fit for the data, and model fit gradually decreases as the measurement of past precariousness is restricted to more recent periods. This implies that precariousness has long-lasting negative effects on the transition to parenthood, and it is of little importance whether a person was recently in a precarious position or whether precariousness was experienced in the more distant past.Economic precariousness has often been suggested to explain postponement of childbearing in developed societies. As precariousness depletes financial resources, increases uncertainty about future employment and income, and engenders stress, it is often thought to cause delays in the transition to parenthood or even to make people put off childbearing altogether  incompatibility of full-time employment and motherhood. This is illustrated by the finding that—after taking into account their past experience of precariousness—women who currently experienced income precariousness had a higher first birth rate than women who did not. Moreover, a particularly low probability of becoming a mother was found among women who had made a transition out of income precariousness, which may be due to a combination of high opportunity costs and a limited accumulation of economic resources in the past . However, some recent studies that have utilized exogenous shocks that cause job losses to come closer to a causal interpretation of the effect of economic precariousness on fertility Below is the link to the electronic supplementary material.


The leading cause of neonatal death worldwide is birth asphyxia. Yearly, in the first month of life, 2.5 million children died around the world. Birth asphyxia is a major problem, particularly in developing nations like Ethiopia. The goal of this study was to determine the magnitude of birth asphyxia and the factors that contributed to it among neonates delivered at the Aykel Primary Hospital in north-central Ethiopia.P < 0.250) for multivariable analysis was determined after data examination and cleaning. Then, to identify important factors of birth asphyxia, a multivariable logistic regression model with a p-value of 0.05 was developed. Finally, a significant relationship between a dependent variable and independent factors was defined as a p-value less than 0.05 with a 95% confidence interval.From August 1 to August 31, 2021, a hospital-based cross-sectional study was conducted on 144 live births. An Apgar score less than 7 in the fifth minute of birth authorized the diagnosis of birth asphyxia. Variable contention . The percentage of neonates that had asphyxia at delivery was 11.11% (95% CI: 6.3 -16.9%). Male newborns were 5.02 times more probable than female newborns to asphyxiate . Mothers who have not had at least one Antenatal Care visit were 3.72 times more likely to have an asphyxiated newborn than those who have at least one Antenatal Care visit . Similarly, mothers who had an adverse pregnancy outcome were 7.03 times more likely to have an asphyxiated newborn than mothers who had no such history .Birth asphyxia in newborn has come to a standstill as a major public health issue. The sexual identity of the newborn, Antenatal Care visits, and a history of poor pregnancy outcomes were all found to be significant risk factors for birth asphyxia. These findings have great importance for various stakeholders who are responsible for reducing birth asphyxia; in addition, policymakers should establish and revise guidelines associated to newborn activities and workshops. The World Health Organization (WHO) defines birth asphyxia as the failure to initiate and maintain breathing after birth .Birth asphyxia occurs when the fetus receives insufficient oxygen, usually during labor and childbirth, resulting in the risk of death  or lifelong disability in the existing infant, and cognitive difficulties can also be predicted due to the pattern of brain injury associated with neonatal encephalopathy , 3.When a newborn has an Apgar score less than seven, it is diagnosed as having birth asphyxia. Scores of four to seven indicate moderate birth asphyxia, while zero to three indicates severe birth asphyxia , 5.Worldwide and yearly, 2.5 million children died in the first month of life which added 47% of deaths of under the age of 5-years and 54% of all under-five deaths occur during the neonatal period among African newborns , 7. In aThe neonatal death rate in Ethiopia is 30 per 1000 live births. With 47/1000 live births, the Amhara region has the highest rate of newborn mortality . The finAs a solution, Ethiopia has developed a variety of initiatives, including expanding ANC coverage, skilled birth attendance, and postnatal care . BecauseA hospital-based cross-sectional study was conducted from August 1 2021 to August 31, 2021.The research was carried out at the Aykel basic hospital in Aykel town, which was founded in 2002 and is located 802 km from Addis Ababa, Ethiopia’s capital city. The hospital includes diverse units; the maternity unit, which has 35 beds, handles more than 3000 clients every year.All live birth neonates gestational age 28 weeks or more in Aykel primary hospitalSource PopulationAll live birth neonate’s gestational age 28 weeks or more at Aykel primary hospital during data collection time.Study PopulationNewborns of unknown gestational age at birth, and newborns with malformationsExclusion Criterian = sample size calculated, Z = level of significance at 95% of confidence interval = 1.96, P = proportion of birth asphyxia from the similar study which was done from Debre Tabor General Hospital (28.35%) . Mothers who had not have at least one ANC visit were 3.72 times more likely than those who had at least one ANC visit to have an asphyxiated newborn . Similarly, mothers with a history of adverse pregnancy outcomes were 7.03 times more likely to have an asphyxiated newborn than those without a history  . When compared to a research conducted in Dira Dawa, Ethiopia (3.1%), it is higher . The posThe possible reasons might be due to the application of updated guidelines, and most studies were referral hospitals while this study was particular to one primary hospital, and this leads to increase number of existence of cases typically birth asphyxia.On the other hand, this study was in line with the study done Jimma Public Hospital Ethiopia (12.5%) , Nigist The magnitude and determinants of birth asphyxia among live newborns at Ayikel Primary Hospital are presented in this report. Birth asphyxia was found to be significantly predicted by sex of the neonate, ANC visit, History of adverse pregnancy outcome.The sex of the newborn was found to be one of the predictors of birth asphyxia in this investigation. A male newborn was 5 times more likely than a female newborn to become asphyxiated. This finding is supported by a study done in sexually dimorphic outcomes , 23, andA mother ANC visit was also a predictor of birth hypoxia. Mothers who did not have at least one ANC visit were 3 times more likely than those who did have at least one ANC visit to have an asphyxiated newborn. A study conducted in Ethiopia systematic review and Meta analysis, Civil Hospital Dow University, Surin Hospital, Soetomo Hospital, and Pattani Hospital Thailand , 24–27 sIn underdeveloped nations, a history of adverse pregnancy outcomes has a significant impact on the occurrence of birth asphyxia for live birth. In this study, mothers who had a history of bad pregnancy outcomes were 7 times more likely to have an asphyxiated baby than mothers who had never had a adverse pregnancy out-comes. Furthermore, this study is supported by a study done in Jimma Public Hospital, Civil Hospital Dow University, Soetomo Hospital, Pattani Hospital Thailand, and University of Gondar Hospital , 27, 29 The study was conducted with a cross-sectional study design, thus it does not prove a cause and effect relationship, and the study was done only live birth which doesn’t include all newborns. In addition, the data were collected within a short period which couldn’t cover annual served activities. To diagnose asphyxia, we evaluated the Apgar score and clinical symptoms. Our Apgar scores are thought to have been issued appropriately by the maternity personnel on hand at the time of delivery. However, using the Apgar score alone to diagnose and predict the result of birth asphyxia has been proved to be unreliable.Birth asphyxia in neonates has come to a standstill as a major public health issue. The sexual identity of the newborn, ANC visits, and a history of poor pregnancy outcomes were all found to be significant risk factors for birth asphyxia. These findings have significant importance for various stakeholders who are responsible for reducing birth asphyxia; in addition, policymakers should establish and revise guidelines associated to newborn activities and workshops. Moreover, researchers use other study design  to recognized left out variables like survival, admission to neonatal unit, need for breathing support, seizures and encephalopathy.


Low-birth-weight infants exhibit a high risk for postnatal morbidity. Cytochrome P450 (CYP) and epoxide hydrolase (EH) are involved in the metabolism of factors responsible for low-birth-weight in infants. Both CYPs and EHs have high substrate specificity and are involved in polyunsaturated fatty acid (PUFA) metabolism. The CYP pathway produces epoxy fatty acids (EpFAs), which are further degraded by soluble EH (sEH). Additionally, sEH inhibition enhances the action of EpFAs and suppresses inflammatory responses. During pregnancy, excessive activation of maternal inflammatory response is a significant factor associated with low-birth-weight. However, the association of EpFAs, which have potential anti-inflammatory properties, with the low-birth-weight of infants remains uninvestigated. This study aimed to clarify the association between the umbilical cord serum EpFA and low-birth-weight using data obtained from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) by analyzing the umbilical cord blood samples.We selected a subgroup of 200 infants (106 boys and 94 girls), quantified EpFA concentration in their cord blood samples collected at birth, and examined its correlation with birth weight.r = −0.101, p = 0.016) as well as LA-derived dihydroxyoctadecenoic acid (diHOME) , 9,10-diHOME , and 12,13-diHOME  after adjusting for obstetric factors, including gestational age, infant’s sex, childbirth history, delivery method, and maternal height.The comparison between the low-birth-weight and normal-birth-weight groups revealed no significant correlation between PUFA and EpFA concentrations, but a significant correlation was observed in the linoleate diol concentrations of the two groups. Furthermore, birth weight did not significantly correlate with PUFA, EpFA, and diol concentrations in cord blood; however, multiple regression analysis showed a significant negative correlation of birth weight with the concentration of linoleic acid (LA) (Birth weight was significantly correlated with the concentration of LA and linoleate diol diHOME after adjusting for obstetric confounders. Our results show that CYP and sEH involved in PUFA metabolism may influence the birth weight of infants. Further validation is needed to provide insights regarding maternal intervention strategies required to avoid low-birth-weight in infants in the future. CYP1A2 C164A polymorphism affect infant birth size (via interaction patterns with SNPs in CYP2E1 and EH 1 (EPHX1)  infants (via three pathways. The cyclooxygenase (COX) and lipoxygenase (LOX) pathways primarily produce inflammatory metabolites  . Additioh weight . Higher  infants –24. Mostabolites . In animabolites , 28. Durabolites , 29–35. We hypothesized that the reduction in the levels of specific EpFA might be responsible for low-birth-weight in infants. Hence, this study aimed to clarify the association between umbilical cord serum EpFA and birth weight using data obtained from the Hamamatsu Birth Cohort for Mothers and Children (HBC) Study by analyzing umbilical cord blood serum samples through liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) according to Lipidome Lab Co., Ltd.This study was conducted as a part of the HBC Study. The details of the cohort setting have been previously reported , 37. OriIn accordance with the Declaration of Helsinki, the study was approved by the Ethics Review Committee of the Hamamatsu University School of Medicine  and the Research Ethics Committee of the University of Fukui. All mothers provided written informed consent for their and their children’s participation in the study.via the venipuncture of the umbilical vein. Subsequently, the samples were kept at room temperature for 30 min and centrifuged at 3500 rpm for 10 min, from which serum was collected and divided into 200 μL aliquots, and then stored at −80°C until analysis . EpFA was separated using a high-performance liquid chromatography system  equipped with an XBridge C18 column  and analyzed on a triple quadrupole mass spectrometer . Mass spectrometric analysis was conducted in negative-ion mode, and fatty acid metabolites were identified and quantified by multiple-reaction monitoring, similar to the determination of other lipid metabolites . For quaThe analytical values lesser than the lower limit of quantitation and detection were below the minimum reliable values for concentration measurement. Therefore, any value below the detection limit was treated as “0” and included in our analysis.Serum levels of interleukins were assayed using a suspension array system . Multiplex kits for measuring interleukins were purchased from Bio-Rad . The kits were used per the manufacturer’s instructions. The serum samples were diluted using the appropriate sample diluents provided in each kit in accordance with the manufacturer’s instructions. Concentrations (pg/ml) of different analytes in the serum samples were determined by using the standard curves generated in the multiplex assays. Each standard curve was generated using eight points of concentrations, and a nonlinear least squares minimization algorithm was used for the curve fitting by the five-parameter logistic equation and to determine the high and low limits of detection. Data points for analytes that were occasionally above or below the detection range were discarded.Data regarding weight at birth, gestational age at birth, sex, and parity of the child were collected from the medical records in the HBC Study. Furthermore, the participating children were divided into the SGA and appropriate-for-gestational age (AGA) groups based on the representative statistics calculated by the Japanese Society of Gynecology and Obstetrics . The infU test was used to compare birth weights between the SGA and AGA groups, and Spearman’s correlation was used to analyze the correlations between birth weight and fatty acids. Birth weight was regressed onto the PUFA metabolites, with gestational age at birth, infant’s sex, parity, delivery method (cesarean section), and maternal height as potential confounders according to previous studies  and 2.060 × 105 pg/mL , respectively  and 7.795 × 105 pg/mL , respectively  ; however, AA-derived EET was 0 pg/mL in 51 samples , but DHA-derived EpDPA was 0 pg/mL in 44 samples  from LA was 1.087 × 10 pg/mL]) Table 2.3 pg/ml      from LA was 1.310 × 10 pg/ml]) Table 2.r = 0.323, p < 0.001, 95% confidence interval [CI] = 0.185–0.448) and maternal height   , AA , EPA , and DHA , showed significant correlations with birth weight , EET , and EpDPA . diHOME , diHETrE , diHETE  and diHDoPE  also showed no significant correlation with birth weight  Table 3.In terms of inflammatory metabolites, we examined the association between interleukin concentrations in cord blood and birth weight, but the correlations were not significant Table 4.r = −0.089, p = 0.223), AA , EPA , and DHA , showed significant correlations with gestational age , EET , and EpDPA  , diHETrE , diHETE , and diHDoPE  also showed no significant correlation   (p = 0.010) (p = 0.003) (p = 0.037) (p = 0.020)  Table 6,r = −0.101, p = 0.016) , 9,10-diHOME , and 12,13-diHOME  concentrations and birth weight , and maternal height, we found that birth weight was significantly correlated with LA concentration (= 0.016) Table 7.Using the multiple regression analysis data from the HBC Study in Japan, we identified the significant association of birth weight with gestational age at birth, maternal height, infant’s sex, parity, delivery method (cesarean section), and umbilical cord serum LA concentration. After adjusting for obstetric confounding factors, birth weight showed a significant negative correlation with LA and diHOME concentrations in cord blood. To the best of our knowledge, the current study is the first to investigate the association of birth weight with EpFA and PUFA metabolism in cord blood.Contrary to our hypothesis, birth weight showed no direct significant correlation with the concentration of any PUFA, EpFA, and diol  in cord blood before adjusting for obstetric confounding factors Table 3.via the CYP pathway affects fetal development . This work was also supported, in part, by Life Science Innovation Center, University of Fukui.We are grateful to the individuals who participated in the study. We would like to thank Ms. Fumiho Yamamoto and Ms. Natsuki Miyagoshi for technical assistance, Ms. Tomoko Taniguchi for clerical support, and Hiroki Nakanishi, PhD, from Lipidome Lab for providing technical advice for this study.Author TO-N was employed by company Lipidome Lab Co., Ltd.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Dyslipidemia may contribute to low bone turnover in patients with type 2 diabetes (T2D) through mediating oxidative stress and atherosclerosis. The low-density lipoprotein cholesterol/apoprotein B (LDL-C/Apo B) ratio is a surrogate marker of small and density low-density lipoprotein cholesterol (sd-LDL-C), a most harmful group of LDL-Cs. The present study aimed to investigate the association between the LDL-C/Apo B ratio and bone turnover in patients with T2D.This study was a cross-sectional study enrolled patients with T2D from January 2021 to December 2021. Each participant was assessed for lipid profiles, bone turnover markers (BTMs), lumbar spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip.p < 0.05). There were no differences in lumbar spine and hip T-score, proportion of osteoporosis  among the three subgroups. The LDL-C/Apo B ratio was positively correlated with lnOC , lnCTx  and lnPINP . These significant positive correlations persisted even when divided into male and female subgroups. Furthermore, three multiple linear regression analyses were constructed to investigate the independent association of the LDL-C/Apo B ratio with the BTMs levels. After adjusting for other clinical parameters, the LDL-C/Apo B ratio was still significantly associated with OC level , CTx level  and PINP level .A total of 335 patients with T2D were enrolled in the study, and the LDL-C/Apo B ratio ranged from 0.78 to 4.00. Along with the LDL-C/Apo B ratio tertile ascending, osteocalcin (OC), C-terminal telopeptide (CTx) and N-terminal propeptide of type-I procollagen (PINP) levels gradually increased (all The LDL-C/Apo B ratio was significantly and positively associated with BTMs in patients with T2D. In clinical practice, more attention should be paid to the patients with T2D whose LDL-C/Apo B ratio is relatively low for the purpose of maintaining bone health. Type 2 diabetes (T2D) and its chronic complications have posed a great threat to global public health, among which bone fragility has attracted more and more attention due to its high incidence, high disability rate and serious impact on quality of life . Bone frIn vitro studies showed that oxidized lipids reduced bone turnover by inhibiting osteoblast differentiation and inducing osteoclast differentiation  was calculated as the weight/height squared. Blood pressure was measured by a standard mercury sphygmomanometer, and the average of three recordings was recorded.2 or a UACR ≥ 30 mg/g lasting more than 3 months (CP which was defined as (fasting glucose × fasting CP)/22.5 was adopted as an indicator of insulin resistance  was calculated as the ratio of urinary albumin to urinary creatinine. Lipid profiles such as triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), LDL-C, apoprotein A (Apo A) and apoprotein B (Apo B) levels, glucose, uric acid (UA), creatinine (Cr) and cystatin C levels were measured using an automated biochemical analyzer  with the inter-assay and intra-assay coefficients of variation (CVs) < 2.8%, and the LDL-C/Apo B ratio was calculated as the ratio of LDL-C to Apo B ratio. According to the CKD-EPI creatinine-cystatin C equation, estimated glomerular filtration rate (eGFR) was calculated (2012) . Chronic3 months . HbA1c lsistance . Serum OThe corresponding CVs from the manufacturers as follows: OC < 2.0%, CTx < 5.4%, PINP < 4.5%, PTH < 4.5%, and vitamin D < 4.0%.The ankle-brachial index (ABI) was detected in each participant using the color Doppler blood flow device  under the operation of an experienced physician. Then peripheral artery disease (PAD) was diagnosed with reference to the Inter-Society Consensus for the Management of Peripheral Arterial Disease guideline and based the ABI values .All participants underwent spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans on Prodigy Scanners  by trained investigators, and the results were analyzed according to the manufacturer’s recommendations. The calculation of T-score was based on the peak BMD in healthy young people of the same race and gender, and the calculation formula of T-score was /standard deviation of peak BMD in healthy young people of the same race and sex. The daily CV value of DXA was controlled below 0.24%. Average T-scores of L1-L4 and T-scores of hips were recorded for further analyses. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip .The total participants were divided into three subgroups based on the LDL-C/Apo B ratio. Kolmogorov-Smirnov test was first conducted to test whether continuous variables conformed to normal distribution. In order to achieve a normal distribution for further analysis, a natural logarithm transformation (ln) was applied, such as lnOC, lnCTX and lnPNIP. The normally and skewed distributed continuous variables and the categorical variables were respectively described as mean ± SD, median (25 and 75% interquartile) and frequencies (percentages). We adopted the one-way analysis of variance, the Kruskal-Wallis test and the chi-square test to compare differences in normally distributed data, skewed distributed data and categorical data, respectively. Pearson’s bivariate correlation analyses were applied to investigate the correlations of the LDL-C/Apo B ratio with BTMs in the total population and separately in men and women. Furthermore, we constructed three multiple linear regression analyses to investigate the independent association of the LDL-C/Apo B ratio with the BTMs levels. Before conducting the linear regression analyses, the case analyses screening outliers were carried out first. If the standardized residual values were not in the range of -3 to 3, the outliers should be considered. Later, the case records were retrieved to exclude the abnormal data as a result of typing errors, and if not, the corresponding data were removed. Data analyses were performed on SPSS statistical software 18.0 . A value of p < 0.05 was defined as statistical significance.p < 0.05). BMI, proportion of peripheral artery disease, statins use, use of acarbose and TG level were the highest in T1, followed by T2 and T3, while TC and Apo B levels were the highest in T3, followed by T2 and T1 . Among the three subgroups, there were significant differences in percentage of hypertension, use of β-blocker and Apo A level . However, there were no differences in age, proportion of males, diabetic duration, systolic/diastolic blood pressure, use of other antidiabetic treatments and other antihypertensive treatments, HbA1c level, HOMA-IRCP level, HDL-C level, LDL-C level, UACR level, eGFR level, proportion of diabetic kidney disease, PTH level, vitamin D level, lumbar spine and hip T-score, proportion of osteoporosis .r = 0.244, 0.226 and 0.211, respectively, all p < 0.001). These significant and positive correlations persisted even when divided into male and female subgroups.As illustrated in 2 = 0.059), lnCTx level  and lnPINP level . After adding the other clinical covariates in each model step by step, the R2 was gradually increased. In the model 1, after adjusting for age, sex, diabetic duration, BMI, systolic/diastolic blood pressure and smoking history, the LDL-C/Apo B ratio was significantly and positively associated with lnOC level , lnCTx level  and lnPINP level . Antidiabetic treatments, antihypertensive treatments and statins medications were then added as clinical covariates in the model 2, and the LDL-C/Apo B ratio was significantly and positively associated with lnOC level , lnCTx level  and lnPINP level . The fully adjusted model 3 further adjusted for HbA1c, HOMA-IRCP and eGFR, the LDL-C/Apo B ratio was still significantly and positively associated with lnOC level , lnCTx level  and lnPINP level .In via multiple linear regression analysis, the LDL-C/Apo B ratio was still significantly and positively associated with serum OC, CTx and PINP level. Collectively, a decreased LDL-C/Apo B ratio is independently associated with low bone turnover in patients with T2D.In the present study, we investigated the association between the LDL-C/Apo B ratio with BTMs in patients with T2D. The main findings are as follows: first, with the increase of the LDL-C/Apo B ratio tertile, serum OC, CTx and PINP levels gradually increased; second, the LDL-C/Apo B ratio was significantly and positively related to serum OC, CTx and PINP levels; third, after adjusting for sex, age, diabetic duration and other clinical factors via DXA for the initial diagnosis of osteoporosis, and osteoporosis is diagnosed based on a T-score lower than or equal to -2.5 at the spine or hip (Existing guidelines recommend detecting BMD (T-score) e or hip . Howevere or hip . A meta-e or hip . These re or hip . Most ste or hip , 24. HenRisk factors for low bone turnover in patients with T2D include glucose control, use of hypoglycemic drugs, hyperlipidemia, advanced glycation end products (AGEs), bone microvascular disease and so on . Poor glin vitro, so oxidized lipids might be positively related to serum CTx level  and the Science and Technology Support Program of Nantong (HS2020005).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.