Associations between birthweight and preterm birth and the ages at menarche and menopause.

BACKGROUND: Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation of the associations between a personal birthweight and/or being born preterm and the age of and menarche and menopause and related events in the Women's Health Initiative, a large, racially and ethnically diverse cohort of postmenopausal women. METHODS: At study entry, women reported their birthweight by category (< 6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, or ≥ 10 lbs.) and preterm birth status (4 or more weeks premature). Ages at events related to menarche and menopause were also self-reported. Linear regression and logistic regression models were used to estimate unadjusted and adjusted effect estimates (ß) and odds ratios (OR), respectively (n ≤ 86,857). Individuals born preterm were excluded from all birthweight analyses. RESULTS: After adjustments, individuals born weighing < 6lbs. were more likely to reach natural menopause at an earlier age (adjusted ß=-0.361, SE = 0.09, P = < 0.001) and have a shorter reproductive window (adjusted ß = -0.287, SE = 0.10, p < 0.004) compared to individuals weighing 6-7 lbs. 15 oz. Individuals born preterm were also more likely to reach natural menopause at an earlier age (adjusted ß=-0.506, SE = 0.16, P = 0.001) and have a shorter reproductive window (adjusted ß = -0.418, SE = 0.17, p < 0.006). CONCLUSIONS: These findings raise concerns that, as more preterm and low birthweight individuals survive to adulthood, the prevalence of earlier-onset menarche and menopause may increase. Clinical counseling and interventions aimed at reducing the incidence of preterm and low birthweight births, as well as intensification of lifestyle modifications to reduce CVD risk among women with these early-life risk factors, should be prioritized.

Maternal mental disorders and neonatal outcomes: Danish population-based cohort study.

BACKGROUND: Previous studies have indicated associations between maternal mental disorders and adverse birth outcomes; however, these studies mainly focus on certain types of mental disorders, rather than the whole spectrum. AIMS: We aimed to conduct a broad study examining all maternal mental disorder types and adverse neonatal outcomes which is needed to provide a more complete understanding of the associations. METHOD: We included 1 132 757 liveborn singletons born between 1997 and 2015 in Denmark. We compared children of mothers with a past (>2 years prior to conception; n = 48 646), recent (2 years prior to conception and during pregnancy; n = 15 899) or persistent (both past and recent; n = 10 905) diagnosis of any mental disorder, with children of mothers with no mental disorder diagnosis before the index delivery (n = 1 057 307). We also considered different types of mental disorders. We calculated odds ratios and 95% CIs of low birthweight, preterm birth, small for gestational age, low Apgar score, Caesarean delivery and neonatal death. RESULTS: Odds ratios for children exposed to past, recent and persistent maternal mental disorders suggested an increased risk for almost all adverse neonatal outcomes. Estimates were highest for children in the 'persistent' group for all outcomes, with the exception of the association between persistent maternal mental disorders and neonatal death (odds ratio 0.96, 0.62-1.48). CONCLUSIONS: Our study provides evidence for increased risk of multiple adverse neonatal outcomes among children of mothers with mental disorders, highlighting the need for close monitoring and support for women with mental disorders.

Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial.

BACKGROUND: Preterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality. METHODS: This is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800-1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted. We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully. DISCUSSION: This pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design. TRIAL REGISTRATION: The study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022.  https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888 .

Neonatal birthweight prediction using two- and three-dimensional estimated fetal weight among borderline small fetuses.

PURPOSE: This study aimed (1) to determine the degree of correlation between 2D and 3D estimated fetal weight (EFW) and neonatal birth weight (BW) among borderline small fetuses and (2) to compare the accuracy and precision of 2D and 3D EFW in BW prediction. METHODS: A retrospective cohort study evaluated fetuses who had an ultrasound performed between January 2017 and September 2021 at a tertiary maternal center. All singleton pregnancies with 3D EFW within 4 weeks of delivery were included. Fetuses with known structural or genetic abnormalities were excluded. Pearson's correlation coefficients were determined for both 2D and 3D EFW to BW then compared using Williams' test and Fisher r to z transformation, where applicable. Mean percent difference and standard deviation were used to assess the accuracy and precision, respectively, of 2D and 3D EFWs in BW prediction. RESULTS: Two hundred forty-eight pregnancies were included. Ultrasound studies were performed with a median interval of 2 weeks (IQR 1, 3) between ultrasound and delivery. Both 2D and 3D estimated fetal weights showed a significant correlation with birth weight (r = 0.74 and r = 0.73, respectively), indicating similar accuracy between the two techniques. CONCLUSION: Two-dimensional and three-dimensional EFWs performed similarly in the prediction of BW in borderline small fetuses.

Predicting newborn birth outcomes with prenatal maternal health features and correlates in the United States: a machine learning approach using archival data.

BACKGROUND: Newborns are shaped by prenatal maternal experiences. These include a pregnant person's physical health, prior pregnancy experiences, emotion regulation, and socially determined health markers. We used a series of machine learning models to predict markers of fetal growth and development-specifically, newborn birthweight and head circumference (HC). METHODS: We used a pre-registered archival data analytic approach. These data consisted of maternal and newborn characteristics of 594 maternal-infant dyads in the western U.S. Participants also completed a measure of emotion dysregulation. In total, there were 22 predictors of newborn HC and birthweight. We used regularized regression for predictor selection and linear prediction, followed by nonlinear models if linear models were overfit. RESULTS: HC was predicted best with a linear model (ridge regression). Newborn sex (male), number of living children, and maternal BMI predicted a larger HC, whereas maternal preeclampsia, number of prior preterm births, and race/ethnicity (Latina) predicted a smaller HC. Birthweight was predicted best with a nonlinear model (support vector machine). Occupational prestige (a marker similar to socioeconomic status) predicted higher birthweight, maternal race/ethnicity (non-White and non-Latina) predicted lower birthweight, and the number of living children, prior preterm births, and difficulty with emotional clarity had nonlinear effects. CONCLUSIONS: HC and birthweight were predicted by a variety of variables associated with prenatal stressful experiences, spanning medical, psychological, and social markers of health and stress. These findings may highlight the importance of viewing prenatal maternal health across multiple dimensions. Findings also suggest that assessing difficulties with emotional clarity during standard obstetric care (in the U.S.) may help identify risk for adverse newborn outcomes.

A Position Modification Device for the Prevention of Supine Sleep During Pregnancy: A Randomised Crossover Trial.

OBJECTIVE: To assess the effectiveness and acceptability of a pillow-like position modification device to reduce supine sleep during late pregnancy, and to determine the impacts on the severity of sleep-disordered breathing (SDB) and foetal well-being. DESIGN: Randomised cross-over study. SETTING AND POPULATION: Individuals in the third trimester of pregnancy receiving antenatal care at a tertiary maternity hospital in Australia. METHODS: Participants used their own pillow for a control week and an intervention pillow for a week overnight, in randomised order. Sleep position and total sleep time for each night of both weeks were objectively monitored, with a sleep study and foetal heart rate monitoring performed on the last night of each week. MAIN OUTCOME MEASURES: Primary outcome = percentage of sleep time in the supine position; secondary outcomes = apnoea-hypopnoea index, foetal heart rate decelerations and birthweight centile. RESULTS: Forty-one individuals were randomised with data collected on 35 participants over 469 nights. There was no difference in percentage of total sleep time in the supine position overnight between the control or intervention pillow week (13.0% [6.1, 25.5] vs. 16.0% [5.6, 27.2], p = 0.81 with a mean difference of 2.5% [95% CI] = -0.7, 5.6, p = 0.12), and no difference in the severity of SDB or foetal heart rate decelerations across weeks. However, increased supine sleep was significantly related to a higher apnoea-hypopnoea index (rs = 0.37, p = 0.003), lower birthweight (rs = -0.45, p = 0.007) and lower birthweight centile (rs = -0.45, p = 0.006). The proportion of supine sleep each night of the week varied widely both within and across participants, despite awareness of side-sleeping recommendations. CONCLUSIONS: We found no evidence to suggest that the adoption of a pillow designed to discourage supine sleep was effective in late pregnancy, with women spending an average of 1 h per night supine. Alternative devices should be investigated, incorporating lessons learnt from this study to inform trials of supine sleep minimisation in pregnancy. TRIAL REGISTRATION: Clinical Trial: (Australia New Zealand Clinical Trials Registry): ACTRN12620000371998.

Development and validation of prediction models for fetal growth restriction and birthweight: an individual participant data meta-analysis.

Background: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. Objectives: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Design: Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Participants: Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Predictors: Maternal clinical characteristics, biochemical and ultrasound markers. Primary outcomes: fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight. Analysis: First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance (c-statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model. Results: Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c-statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g). Limitations: We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data. Future work: International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation. Conclusion: The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management. Study registration: This study is registered as PROSPERO CRD42019135045. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

One in ten babies is born small for their age. A third of such small babies are considered to be 'growth-restricted' as they have complications such as dying in the womb (stillbirth) or after birth (newborn death), cerebral palsy, or needing long stays in hospital. When growth restriction is suspected in fetuses, they are closely monitored and often delivered early to avoid complications. Hence, it is important that we identify growth-restricted babies early to plan care. Our goal was to provide personalised and accurate estimates of the mother's chances of having a growth-restricted baby and predict the baby's weight if delivered at various time points in pregnancy. To do so, first we tested how accurate existing risk calculators ('prediction models') were in predicting growth restriction and birthweight. We then developed new risk-calculators and studied their clinical and economic benefits. We did so by accessing the data from individual pregnant women and their babies in our large database library (International Prediction of Pregnancy Complications). Published risk-calculators had various definitions of growth restriction and none predicted the chances of having a growth-restricted baby using our definition. One predicted baby's birthweight. This risk-calculator performed well, but underpredicted the birthweight by up to 143 g. We developed two new risk-calculators to predict growth-restricted babies (International Prediction of Pregnancy Complications-fetal growth restriction) and birthweight (International Prediction of Pregnancy Complications-birthweight). Both calculators accurately predicted the chances of the baby being born with growth restriction, and its birthweight. The birthweight was underpredicted by <9.7 g. The calculators performed well in both mothers predicted to be low and high risk. Further research is needed to determine the impact of using these calculators in practice, and challenges to implementing them in practice. Both International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight risk calculators will inform healthcare professionals and empower parents make informed decisions on monitoring and timing of delivery.

Adverse pregnancy outcomes in maternal malarial infection: A systematic review and meta-analysis.

Background: Malaria in pregnancy is a critical public health issue that can lead to severe adverse outcomes for both mother and fetus. This systematic review and meta-analysis evaluated the prevalence of adverse birth outcomes in malaria-infected pregnancies and examines their association with the condition. Method: We searched databases up to January 30, 2024, for observational studies on pregnant women with malaria. Data were analyzed using a random-effects model to calculate pooled prevalence rates and risk ratios (RRs) for adverse outcomes, with statistical support from R software version 4.3. Results: Thirty-one studies were included, showing high prevalence of low birth weight (LBW; 17.4 %), preterm birth (17.9 %), and small for gestational age (SGA; 16.1 %) in malaria-affected pregnancies. Infected mothers were significantly more likely to have LBW infants (RR = 1.755), preterm births (RR = 1.484), and SGA infants (RR = 1.554). The risk of stillbirth was not significantly increased (RR = 1.238). Conclusion: Malaria in pregnancy significantly elevates the risk of LBW, preterm birth, and SGA, underscoring the need for effective malaria prevention and treatment strategies in endemic regions. Future research should aim to refine and implement these strategies to enhance maternal and neonatal health outcomes.

Association between neonatal mortality and births not weighed among 400 thousand institutional deliveries in 32 low- and middle-income countries.

BACKGROUND: Low birthweight (LBW) children have a higher risk of neonatal mortality. All institutional deliveries, therefore, should be weighed to determine appropriate care. Mortality risk for newborns who are not weighed at birth (NWB) is unknown. METHODS: This paper used logit regression models to compare the odds of death for NWB neonates to that of other neonates using data on 401 712 institutional births collected in Demographic and Health Surveys from 32 low- and middle-income countries. RESULTS: In the pooled sample, 2.3% died in the neonatal period and 12% were NWB. NWB neonates had a high risk of mortality compared to normal birthweight children (Adjusted odds ratio [AOR] 5.8, 95% CI: 5.3, 6.5). The mortality risk associated with NWB was higher than for LBW. The neonatal mortality risk associated with NWB varied across countries from AOR of 2.1 (95% CI: 1.22, 3.8) in Afghanistan to 94 (95% CI: 22, 215) in Gabon. In the pooled sample, the 12% of children who were NWB accounted for 37% of all neonatal deaths. CONCLUSIONS: The association between NWB and neonatal mortality may suggest a need to focus on the quality of institutions related to newborn care. However, further studies are needed to determine causality. A health emergency or death may also cause NWB.

Job strain and adverse pregnancy outcomes: A scoping review and meta-analysis.

BACKGROUND: Previous studies have shown that job strain is associated with low birthweight (LBW), preterm birth (PTB), and small for gestational age (SGA). We conducted a scoping review and meta-analysis to assess the association between job strain and adverse pregnancy outcomes. METHODS: A literature search was performed on PubMed. We included English-language studies that examined the association between job strain (based on the Karasek demand-control model) and pregnancy outcomes. We excluded letters, posters, reviews, and qualitative studies. Random effects meta-analysis was performed. Heterogeneity was assessed using τ2 and I2 statistics. Potential bias was assessed using standard funnel plots. Asymmetry was evaluated by Egger's test. Leave-one-out analysis was performed for sensitivity analyses. RESULTS: Three eligible studies were found for LBW, seven for PTB, and four for SGA. The number of subjects ranged from 135 to 4889, and the prevalence of high job strain ranged from 6.64% to 33.9%. The pooled odds ratio and 95% confidence interval (CI) for LBW, PTB, and SGA were 1.23 (95% CI: 0.97, 1.56), 1.10 (95% CI: 1.00, 1.22), and 1.16 (95% CI: 0.97, 1.39) respectively, indicating modest associations. Heterogeneity for LBW and PTB may not be important but may be moderate for SGA. No publication bias was detected for LBW and PTB, but possible publication bias exists for SGA. CONCLUSION: We found a modest association between job strain and PTB. Since job strain is only one of the many aspects of an unhealthy work environment, interventions that improve working conditions more broadly are needed.

Disease burden comparison and associated risk factors of early- and late-onset neonatal sepsis in China and the USA, 1990-2019.

BACKGROUND: The morbidity and mortality rates of neonatal sepsis are high, with significant differences in risk factors and disease burden observed between developing and developed countries. OBJECTIVE: To provide evidence to support recommendations on improving public health policies using a comparative systematic analysis of the disease burden. METHODS: Using data from the Global Burden of Disease Study 2019, the prevalence and incidence of early- and late-onset neonatal sepsis and the disability-adjusted life years (DALYs) due to both countries in both China and the United States of America (USA) were assessed. Furthermore, the DALYs and summary exposure values for the primary risk factors (short gestation and low birthweight) were analysed. Joinpoint regression models were used to analyse temporal trends in epidemiological indicators of neonatal sepsis. RESULTS: Between 1990 and 2019, the incidence and prevalence of neonatal sepsis demonstrated a significant upwards trend in China, whereas both were largely stable in the USA. A decreasing trend in the DALYs due to neonatal sepsis caused by short gestation and low birthweight in both sexes was observed in both countries, whereas a fluctuating increasing trend in years lived with disability was observed in China. CONCLUSIONS: The aim of the Chinese public health policy should be to control risk factors, learning from the advanced health policy planning and perinatal management experiences of developed countries.

Main findings Disability-adjusted life years (DALYs) attributed to short gestation and low birth-weight for neonatal sepsis have been decreasing in both China and the USA; years lived with disability (YLDs) and summary exposure values (SEVs) have been increasing in China.Added knowledge This study provides new knowledge about the disease burden of neonatal sepsis attributable to short gestation and low birthweight and suggests possible interventions.Global health impact for policy and action Public health policies in developing countries need to focus on moderating risk factors, learning from the advanced health policy planning and perinatal management experiences of developed countries, and improving neonatal follow-up and rehabilitation interventions.

A randomized-controlled trial of parent-administered interventions to improve short-term motor outcomes in hospitalized very low birthweight infants.

BACKGROUND: Premature infants are at increased risk for cerebral palsy (CP). Early interventions with a motor focus and administered by parents may improve motor outcomes. AIMS: Secondary study evaluating the short-term motor outcomes and risk for CP in very low birthweight (VLBW) infants randomized to multimodal interventions with a motor focus provided by parents versus usual care. STUDY DESIGN: Randomized controlled trial (intervention vs. usual care (control group)). SUBJECTS: Infants (<32 weeks' gestational age (GA) and/or <1500 grams birthweight) born between March 2019 and October 2020. OUTCOME MEASURES: Short-term motor outcomes and risk for CP was evaluated using the Hammersmith Infant Neurological Evaluation (HINE, primary motor outcome), the General Movement Assessment (GMA) and the Test of Infant Motor Performance (TIMP) at 3 months' postmenstrual age (PMA). RESULTS: 70 participants were enrolled (GA 28.3±2.7 weeks, birthweight 1139.2±376.6 grams, 64.3% male). The in-person follow-up rate was 73%, lower than expected, in part due to COVID-19 restrictions, resulting in 25 infants (intervention) and 26 infants (control) with outcome data available for analysis. There was not a significant difference in the HINE, GMA or TIMP at 3 months' PMA between groups. CONCLUSION: Multimodal interventions with a motor focus and provided by parents need further investigation to determine if they can improve short-term motor outcomes in VLBW infants. These interventions are evidence-based and the evaluation of broader implementation into routine care is also needed.

A swallowing and breastfeeding intervention programme for small and sick neonates embedded in kangaroo mother care.

Available evidence of oral sensorimotor interventions for small neonates is not strong. Evidence of interventions for sick term neonates is largely lacking. Studies are limited by risk of bias and inconsistency. Evidence of interventions relying on a single stimulation technique only appears to be low to very low. Ongoing research is required.Contribution: We describe a five-component neonatal swallowing and breastfeeding intervention programme embedded in the practice of kangaroo mother care (KMC). Drawing on oropharyngeal physiology, neonatology, neurodevelopmental care, breastfeeding- and KMC science, the programme is the product of collaboration between a speech-language therapist and a medical doctor, and their team. Its implementation is dependent on coaching mothers and the neonatal care team. Researchers are invited to determine outcomes of the programme.

Birthweight influences liver structure, function and disease risk: Evidence of a causal association.

AIM: Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators. RESULTS: When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%). CONCLUSIONS: Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.

Prediction of intrapartum caesarean section in vaginal breech birth: development of models for nulliparous and multiparous women.

OBJECTIVES: To develop prediction models for intrapartum caesarean section in vaginal breech birth. METHODS: This single-center cohort-study included 262 nulliparous and 230 multiparous women attempting vaginal breech birth. For both groups, we developed and (internally) validated three models for the prediction of intrapartum cesarean section. RESULTS: The prediction model for nulliparous women (AUC: 0.67) included epidural analgesia (aOR 2.14; p=0.01), maternal height (aOR 0.64 per 10 cm; p=0.08), birthweight ≥3.8 kg (aOR 2.45; p=0.03) and an interaction term describing the effect of OC if birthweight is ≥3.8 kg (aOR 0.24; p=0.04). An alternative model for nulliparous women which, instead of birthweight, included fetal abdominal circumference with a cut-off at 34 cm (aOR 1.93; p=0.04), showed similar performance (AUC: 0.68). The prediction model for multiparous women (AUC: 0.77) included prelabor rupture of membranes (aOR 0.31; p=0.03), epidural analgesia (aOR 2.42; p=0.07), maternal BMI (aOR 2.92 per 10 kg/m2; p=0.01) and maternal age (aOR 3.17 per decade; p=0.06). CONCLUSIONS: Our prediction models show the most relevant risk factors associated with intrapartum cesarean section in vaginal breech birth for both nulliparous and multiparous women. Importantly, this study clarifies the role of the OC by showing that this parameter is only associated with intrapartum cesarean section if birthweight is above 3.8 kg (or abdominal circumference is above 34 cm). Conversely, knowing the OC when the birthweight is less than 3.8 kg (or abdominal circumference is less than 34 cm) did not improve prediction of this surgical outcome.

The effect of repeated lipopolysaccharide endotoxin challenge on immune response of breeding ewes and subsequent lamb performance.

Infectious disease caused by exposure to Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is recognized to suppress female fertility. However, the effect of varying low-dose endotoxin exposure during distinct stages of follicle development on immune response, reproductive performance, and lamb performance has yet to be elucidated. Therefore, the objective of this study was to evaluate acute phase response, mRNA abundance of inflammatory markers, reproductive performance and lamb growth characteristics of ewes challenged with subclinical doses of LPS. Rambouillet ewes (n = 36; 68.2 ± 1.1 kg; age 3 to 7 yr) stratified by body weight (BW) and age were assigned to treatment groups. Ewes received subcutaneous injections of saline (CON, n = 12), 1.5 µg/kg BW LPS (LOW, n = 12), or 3.0 µg/kg BW LPS (HIGH, n = 12) on days 5, 10, and 15 of a synchronized follicular wave. Ewes were subsequently placed with a raddle-painted ram on day 16 for a 35-d breeding season. On treatment days 5 and 15, blood samples, peripheral blood leukocytes, and rectal temperature were collected before and at regular intervals for 12 h after LPS challenge. Immune response to LPS was confirmed by increased temperature and serum cortisol concentrations on days 5 and 15. Endotoxin increased circulating plasma concentration of the acute phase protein, haptoglobin by greater than 15%, in both LPS-treated groups on days 5 and 15 at 12 h compared with control (P≤ 0.05). Pro- and anti-inflammatory mRNA gene expression demonstrated no differences in expression for tumor necrosis factor-α or peroxisome proliferator-activated receptor gamma among treatment groups (P > 0.10). Likewise, Toll-like receptor 4 (TLR4), interleukin-8 (IL-8), and superoxide dismutase 2 (SOD2) expression was similar among treatment groups on day 5. However, ewes challenged with LPS on day 15 displayed greater mRNA expression for TLR4 from 2 to 6 h (P < 0.05), a 7-fold increase for IL-8 from 1.5 to 2.5 h (P < 0.05), and 8-fold induction for SOD2 from 2 to 6 h (P < 0.05) as compared with controls. First service conception rates were 90% for control ewes and 75% for both treated groups (P â€…= 0.84). Treated ewes demonstrated a reduction in lamb birth weight compared with controls (P ≤ 0.05) and a tendency for reduction of 60-d adjusted weaning weight (P = 0.09). Data suggest that subacute endotoxin exposure aligning with key follicle and oocyte maturation events results in detrimental growth performance of the subsequent lamb.

During disease states, bacterial endotoxins act locally and systemically, negatively impacting reproductive capacity and economic productivity. The present study investigated the impacts of repeated low-dose endotoxin exposure during follicular development on the immune response and subsequent reproductive and lamb growth variables. Results indicate that bacterial endotoxin challenge during follicular development and oocyte maturation leads to reduced lamb birth weight and 60-d adjusted weaning weight.

Radiographic scores as a predictor of oxygenation index in very low-birthweight infants.

BACKGROUND: Very low birthweight infants (VLBWIs) often undergo chest radiographic examinations without standardization or objectivity. This study aimed to assess the association of two radiographic scores, the Brixia and radiographic assessment of lung edema (RALE), with oxygenation index (OI) in ventilated VLBWIs and to determine the optimal cutoff values to predict hypoxic respiratory severity. METHODS: VLBWIs who received invasive respiratory support with arterial lines between January 2010 and October 2023 were enrolled in this study (n = 144). The correlation between the Brixia or RALE scores and OI was investigated. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff points of the two radiographic scores for predicting OI values (OI ≥5, ≥10, and ≥15). RESULTS: The enrolled infants had a median gestational age of 27 weeks (interquartile range [IQR], 25-28 weeks) and a median birthweight of 855 g (IQR, 684-1003 g). Radiographic scoring methods correlated with the OI (Brixia score: r = 0.79, p < 0.001; RALE score: r = 0.72, p < 0.001). The optimal cutoff points for predicting OI values were as follows: Brixia score: OI ≥5, 10; OI ≥10, 13; OI ≥15, 15; RALE score: OI ≥5, 22; OI ≥10, 31; and OI ≥15, 40. CONCLUSIONS: Brixia and RALE scores are useful predictive markers of the oxygenation status in intubated VLBWIs with stable hemodynamics. These scores are easy to use and promising tools for clinicians to identify patients with a higher risk of hypoxic respiratory failure.

Hypertension subtypes and adverse maternal and perinatal outcomes - a retrospective population-based cohort study.

BACKGROUND: This study aims to examine risk of adverse pregnancy outcomes and mothers' characteristics in patients with chronic hypertension, gestational hypertension and preeclampsia. METHODS: The study included all births born from women aged 15-45 years, in Lleida, Spain from 2012 to 2018. Pregnancy outcomes were retrieved by regional administrative databases. Logistic regression analysis was used to calculate adjusted odds ratios (OR) (OR 95% CI) for maternal characteristics or neonatal outcomes. RESULTS: Among 17,177 pregnant women, different types of hypertension present varying risks for both the mother and fetus. There is an increased risk of cesarean section in patients with preeclampsia (OR 2.04, 95% CI: 1.43-2.88). For the newborn, a higher risk of preterm birth is associated with maternal chronic hypertension (OR 3.09, 95% CI: 1.91-4.83) and preeclampsia (OR 5.07, 95% CI: 3.28-7.65). Additionally, there is a higher risk of low birth weight in cases of maternal chronic hypertension (OR 3.2, 95% CI: 2.04-4.88), preeclampsia (OR 5.07, 95% CI: 3.34-7.52), and gestational hypertension (OR 2.72, 95% CI: 1.49-4.68). Furthermore, only newborns of patients with preeclampsia had a higher risk of an Apgar score lower than 7 in the first minute (OR 2.95, 95% CI: 1.45-5.38). CONCLUSIONS: In the study population adjusted for body weight, the different types of hypertension represent different risks in the mother and foetus. These complications were mostly associated with preeclampsia.

Association between Liver and Kidney Function and Birth Outcomes in Pregnant Surinamese Women Exposed to Mercury and Lead in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) Environmental Epidemiologic Cohort Study.

Exposure to mercury (Hg) and lead (Pb), in combination with liver and kidney impairment, may result in adverse birth outcomes. From 408 women in the age range of 16 to 46 years, living in rural and urban areas in the interior of Suriname, we looked at the association between adverse birth outcomes and exposure to Hg and Pb in combination with liver and kidney function. This group of women represented a subcohort of pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH)-Meki Tamara study. Liver function was assessed by measuring aspartate amino transferase (AST), alanine amino transferase (ALT), and gamma-glutamyl transferase (GGT). Kidney function was assessed by measuring creatinine, urea, and cystatin C. We defined preterm births as birth before 37 weeks of gestation, low birthweight as birthweight < 2500 g, and low Apgar score as a score < 7 at 5 min, and these were used as indicators for adverse birth outcomes. Small size for gestational age was defined as gestational age < -2SD weight for GA. We found significant statistical associations between biomarkers for liver and kidney functions and adverse birth outcomes Apgar score and gestational age. No significant association was found between heavy metals Hg and lead and adverse birth outcomes.

Genetic associations of birthweight, childhood, and adult BMI with metabolic dysfunction-associated steatotic liver disease: a Mendelian randomization.

PURPOSE: The causal relationship between life course adiposity with metabolic dysfunction-associated steatotic liver disease (MASLD) is ambiguous. We aimed to investigate whether there is an independent genetic causal relationship between body size at various life course and MASLD. METHODS: We performed univariable and multivariable Mendelian randomization (MR) to estimate the causal effect of body size at different life stages on MASLD (i.e., defined by the clinical comprehensive diagnosis from the electronic health record [HER] codes [ICD9/ICD10] or diagnostic phrases), including birthweight, childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP). RESULTS: In univariate analyses, higher genetically predicted lower birthweight (ORIVW = 0.61, 95%CI, 0.52 to 0.74), Childhood BMI ( ORIVW = 1.37, 95%CI, 1.12 to 1.64), and adult BMI (ORIVW = 1.41, 95%CI, 1.27 to 1.57) was significantly associated with subsequent risk of MASLD after Bonferroni correction. The MVMR analysis demonstrated compelling proof that birthweight and adult BMI had a direct causal relationship with MASLD. However, after adjusting for birthweight and adult BMI, the direct causal relationship between childhood BMI and MASLD disappeared. CONCLUSION: For the first time, this MR elucidated new evidence for the effect of life course adiposity on MASLD risk, providing lower birthweight and duration of obesity are independent risk factors for MASLD. Our findings indicated that weight management during distinct time periods plays a significant role in the prevention and treatment of MASLD.