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Background Micronutrient deficiencies among pregnant women remain highly prevalent in low and middle-income countries. Multiple micronutrient supplementation (MMS) has been proven more beneficial than standard iron-folic acid supplementation in reducing adverse pregnancy outcomes. Limited data on adherence to MMS in pregnant women in programmatic settings is available. Therefore, our study aims to assess adherence to the recommended intake of a multiple micronutrient supplement (UNIMMAP-MMS) in relation to demographic characteristics alongside a community-based MMS program. Method A prospective longitudinal study was performed in the Parepare district, South Sulawesi province, Indonesia, including 1216 participants. MMS was provided at the first antenatal care visit and women were followed up until delivery. The number of MMS tablets consumed, the start of MMS intake and information regarding possible intake determinants were recorded. Adherence was defined as ≥ 90 tablets. Binary logistic regression was used to assess associations between characteristics of women and adherence. Results Among the 655 women (53.9%) who started MMS intake in the first trimester, approximately 90% continued using MMS in the following trimesters and 75.3% consumed MMS ≥ 90 tablets. Among the 41.2% of women who started in the second trimester, 90% continued intake in the third trimester and 32.3% consumed ≥ 90 tablets. Only 4.9% started MMS in the third trimester. Overall adherence to MMS was 53.9%. Factors that impacted MMS intake were pregnancy interval ≤ 2y (AOR = 0.65, 95% CI 0.46, 0.92), start of MMS use in the second trimester and third trimester (AOR = 0.15, 95% CI 0.12, 0.20) and (AOR = 0.01, 95% CI 0.00, 0.04) respectively, being overweight (AOR = 1.44, 95% CI 1.04, 2.00) and experiencing no side effects (AOR = 3.46, 95% CI 1.82, 6.58). Conclusion Implementation of MMS via community health centers resulted in high adherence once supplementation started. As many women started MMS late, attention to antenatal visit planning earlier in pregnancy can be further improved.

In this randomized trial, rates of vaginal birth of a healthy singleton at 2 years of follow-up were not higher among obese women who received a 6-month lifestyle intervention before infertility treatment than among those who received prompt infertility treatment. Obesity is a major public health problem. 1 In most developed countries, 14 to 20% of women of reproductive age are obese (body-mass index [BMI; the weight in kilograms divided by the square of the height in meters], ≥30), whereas in some countries, the prevalence of obesity is as high as 60%. 1 Obesity negatively affects female reproductive health because it is associated with increased risks of menstrual dysfunction, anovulation, and infertility. 2 – 4 Success rates with ovulation induction and assisted reproductive techniques are lower among obese infertile women than among normal-weight women. 5 , 6 The risks of miscarriage, 6 , 7 gestational diabetes, hypertensive disorders, . . .

Preeclampsia is a potentially life-threatening pregnancy complication. Among women whose pregnancies are complicated by preeclampsia, the Preeclampsia Integrated Estimate of RiSk (PIERS) models (i.e., the PIERS Machine Learning [PIERS-ML] model, and the logistic regression-based fullPIERS model) accurately identify individuals at greatest or least risk of adverse maternal outcomes within 48 h following admission. Both models were developed and validated to be used as part of initial assessment. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recommends repeated use of such static models for ongoing assessment beyond the first 48 h. This study evaluated the models' performance during such consecutive prediction. This multicountry prospective study used data of 8,843 women (32% white, 30% black, and 26% Asian) with a median age of 31 years. These women, admitted to maternity units in the Americas, sub-Saharan Africa, South Asia, Europe, and Oceania, were diagnosed with preeclampsia at a median gestational age of 35.79 weeks between year 2003 and 2016. The risk differentiation performance of the PIERS-ML and fullPIERS models were assessed for each day within a 2-week post-admission window. The PIERS adverse maternal outcome includes one or more of: death, end-organ complication (cardiorespiratory, renal, hepatic, etc.), or uteroplacental dysfunction (e.g., placental abruption). The main outcome measures were: trajectories of mean risk of each of the uncomplicated course and adverse outcome groups; daily area under the precision-recall curve (AUC-PRC); potential clinical impact (i.e., net benefit in decision curve analysis); dynamic shifts of multiple risk groups; and daily likelihood ratios. In the 2 weeks window, the number of daily outcome events decreased from over 200 to around 10. For both PIERS-ML and fullPIERS models, we observed consistently higher mean risk in the adverse outcome (versus uncomplicated course) group. The AUC-PRC values (0.2-0.4) of the fullPIERS model remained low (i.e., close to the daily fraction of adverse outcomes, indicating low discriminative capacity). The PIERS-ML model's AUC-PRC peaked on day 0 (0.65), and notably decreased thereafter. When categorizing women into multiple risk groups, the PIERS-ML model generally showed good rule-in capacity for the \"very high\" risk group, with positive likelihood ratio values ranging from 70.99 to infinity, and good rule-out capacity for the \"very low\" risk group where most negative likelihood ratio values were 0. However, performance declined notably for other risk groups beyond 48 h. Decision curve analysis revealed a diminishing advantage for treatment guided by both models over time. The main limitation of this study is that the baseline performance of the PIERS-ML model was assessed on its development data; however, its baseline performance has also undergone external evaluation. In this study, we have evaluated the performance of the fullPIERS and PIERS-ML models for consecutive prediction. We observed deteriorating performance of both models over time. We recommend using the models for consecutive prediction with greater caution and interpreting predictions with increasing uncertainty as the pregnancy progresses. For clinical practice, models should be adapted to retain accuracy when deployed serially. The performance of future models can be compared with the results of this study to quantify their added value.

Background Postoperative pulmonary complications (PPCs) are the most commonly reported complications after esophagectomy. The aim of this study was to examine the effect and feasibility of preoperative inspiratory muscle training-high intensity (IMT-HI), and IMT-endurance (IMT-E) on the incidence of PPCs in patients following esophagectomy for esophageal cancer (EC). Method A single-blind, randomized, clinical pilot study was conducted between 2009 and 2012. Forty-five participants were assigned to either IMT-HI or IMT-E. Effectiveness was assessed by analyzing PPCs, length of hospital stay (LOS), duration of mechanical ventilation, stay on the intensive care unit, and number of reintubations. Maximal inspiratory pressure and lung function changes were recorded pre- and post-training. Feasibility was assessed by IMT-related adverse events, training compliance, and patients’ satisfaction. Results Thirty-nine patients could be analyzed, 20 patients in the IMT-HI arm and 19 patients in the IMT-E arm. The incidence of PPCs differed significantly between groups and was almost three times lower for the IMT-HI group (4 vs. 11 patients; p  = 0.015). Other differences in favor of the IMT-HI group were LOS (13.5 vs. 18 days; p  = 0.010) and number of reintubations (0 vs. 4 patients; p  = 0.030). Both interventions proved to be equally feasible. Conclusion Preoperative IMT-HI showed to be a promising, effective, and feasible intervention to reduce PPCs in EC patients undergoing esophagectomy. Further research with a larger sample size is recommended.

Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.

PurposeThe Lifelines Reproductive Origins of Adult Health and Disease (Lifelines-ROAHD) cohort provides a uniquely detailed dataset allowing investigations of determinants of reproductive health as well as the influence of reproductive events on future health and disease of mother and child(ren). Lifelines-ROAHD cohort is embedded in the population-based Lifelines cohort study.ParticipantsIn total, 5412 women of reproductive age (20–45 years) were included in the Lifelines-ROAHD cohort, in the period 2017–2018.Findings to dateIn the population, 45.6% of the women indicated that they had a natural menstrual cycle. In total, 908 women (16.8%) consulted a healthcare provider for infertility; subsequently diagnosed fertility problems were anovulation (24.4%), male partner infertility problems (22.5%) or unexplained infertility (22.2%). Women underwent various consecutive assisted reproductive treatments, for example, ovulation induction (19.8%) or in vitro fertilisation (5.4%). In total, 2808 women experienced 6158 pregnancies and 5068 births. Adverse pregnancy outcomes were miscarriage (14.3%), ectopic pregnancy (0.9%) or termination of pregnancy or medical abortion (2.0 %). The modes of delivery were vaginal births (74.9%), instrumental vaginal births (11.9%), elective caesarean section (3.9%) and emergency caesarean section (9.3%). Birth outcomes were born alive at term (93.6%), born alive (very) pre-term (5.8%), stillbirth (0.316%) and neonatal death (0.197%). Additional data about 2660 most recent pregnancies showed that 19.9% of the women had irregular working hours. One year postpartum, women indicated adverse physical health issues in one or more domains, range 0.5%–12.5%. They also indicated adverse psychological health issues in one or more domains, range 0.7%–1.6%, and 1.6% experienced diminished sexual health.Future plansDue to the embedding of Lifelines-ROAHD cohort in the original Lifelines cohort, the women will be longitudinally followed. Additionally, we aim to collect data with a second online questionnaire aiming to complete women’s reproductive histories, by collecting data about potential first and subsequent pregnancies conceived after the date of completion of baseline Lifelines-ROAHD cohort.

In low-income countries, where socioeconomic adversities and perinatal distress are common, adverse birth outcomes are significant public health problems. In these settings, perinatal distress, i.e., high symptoms of anxiety, depression, and/or stress during pregnancy, may be linked with adverse birth outcomes. However, few prospective studies have investigated the impact of perinatal distress on adverse birth outcomes such as preterm birth (gestational age <37 weeks), low birth weight (<2.5 kg), and small for gestational age birth (birth weight below the 10th percentile for gestational age and sex). Our main objective was to assess the influence of perinatal distress on adverse birth outcomes. Secondly, to investigate if perinatal distress is an independent risk factor or a mediator in the pathway between socioeconomic adversity and adverse birth outcomes. In a prospective cohort study following 991 women from before 20 weeks of gestation until delivery in northern Ethiopia, we collected self-reported data on distress at a mean of 14.8 (standard deviation [SD] = 1.9) and 33.9 (SD = 1.1) weeks of gestation. Distress was measured using the Edinburgh Postnatal Depression Scale, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Perceived Stress Scale. To determine birth outcomes, gestational age was estimated from the last menstrual period, fundal palpation, and/or ultrasound, while birth weight was obtained from delivery records and measured within three days after birth for those delivered at home. Logistic regression and mediation analysis were employed to evaluate the impact of perinatal distress on adverse birth outcomes. Perinatal anxiety (OR [95% CI] 1.08 [1.02, 1.13]), depression (1.07 [1.03, 1.11]), stress (1.14 [1.07, 1.22]), and total distress (1.15 [1.07, 1.23]) were all associated with low birth weight, and small for gestational age birth but none did with preterm birth. Mediation analysis demonstrated that perinatal distress was a mediator in the pathway between socioeconomic adversity and adverse birth outcomes. Our study revealed that perinatal distress was linked with adverse birth outcomes and acted as a mediator between socioeconomic adversity and these outcomes. Our findings highlight the importance of screening women for distress and providing appropriate interventions, focusing on women experiencing socioeconomic adversity. Integrating mental health services into primary maternal care in low-income countries could be an effective approach to achieve this.

Background Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine‐based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of serum creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision‐making. Methods We included 8437 community‐dwelling adults enrolled in the Dutch PREVEND study and 5033 in the US NHANES replication cohort. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification. Results Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1–Q3) serum creatinine and cystatin C were 71 (61–80) and 80 (62–88) μmol/L and 0.87 (0.78–0.98) and 0.91 (0.80–1.10) mg/L, respectively. Higher serum creatinine was associated with greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1636 (19%) deaths were registered over a median follow‐up of 12.9 (5.8–16.3) years with a 10‐year mortality rate (95% CI) of 7.6% (7.1–8.2%). In the NHANES, 1273 (25%) deaths were registered over a median follow‐up of 17.9 (17.3–18.5) years with a 10‐year mortality rate of 13.8% (12.8–14.7%). Both markers were associated with increased mortality. Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality, while the association between serum cystatin C and increased mortality strengthened. The shapes of the associations in the PREVEND study and NHANES were almost identical. Conclusions The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.

Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial was to determine the diagnostic value of I-FABP measured in plasma (I-FABPp) and urine (I-FABPu) for the presence of NEC, to evaluate I-FABP levels during NEC development, and to assess its prognostic value for the progression from suspected to complicated disease. Between 2010 and 2012 we prospectively enrolled neonates with suspected NEC. We measured I-FABP levels eight-hourly from onset of suspected NEC for at least 48 hours, or until surgery. NEC diagnosis was confirmed radiologically or during operation. We defined NEC as complicated if it resulted in surgery and/or death. We determined disease course and diagnostic I-FABP cut-off points. The study comprised 37 neonates (24M, 13F), gestational age 28 (24-36) weeks, birth weight 1190 (570-2,400) grams. We found significantly higher I-FABPp and I-FABPu levels in NEC patients (n = 22) than in patients with other diagnoses (n = 15). Cut-off values for diagnosing NEC were 9 ng/mL I-FABPp and 218 ng/mL I-FABPu, with corresponding likelihood ratios (LRs) of 5.6 (95% CI 0.89-35) and 5.1 (95% CI 0.73-36), respectively. I-FABP levels were highest in the first eight hours after symptom onset and gradually decreased over time. Cut-off values for complicated disease were 19 ng/mL I-FABPp and 232 ng/mL I-FABPu, with LRs of 10 (95% CI 1.6-70) and 11 (95% CI 1.6-81), respectively. Both plasma and urinary I-FABP levels specifically identify NEC in preterm infants prior to appearance of diagnostic radiological signs suggestive for NEC. Moreover, serial I-FABP measurements accurately predict development of complicated disease.

Background A history of stillbirth is a risk factor for recurrent fetal death in a subsequent pregnancy. Reported risks of recurrent fetal death are often not stratified by gestational age. In subsequent pregnancies increased rates of medical interventions are reported without evidence of perinatal benefit. The aim of this study was to estimate gestational-age specific risks of recurrent stillbirth and to evaluate the effect of obstetrical management on perinatal outcome after previous stillbirth. Methods A retrospective cohort study in the Netherlands was designed that included 252.827 women with two consecutive singleton pregnancies (1 st and 2 nd delivery) between 1999 and 2007. Data was obtained from the national Perinatal Registry and analyzed for pregnancy outcomes. Fetal deaths associated with a congenital anomaly were excluded. The primary outcome was the occurrence of stillbirth in the second pregnancy stratified by gestational age. Secondary outcome was the influence of obstetrical management on perinatal outcome in a subsequent pregnancy. Results Of 252.827 first pregnancies, 2.058 pregnancies ended in a stillbirth (8.1 per 1000). After adjusting for confounding factors, women with a prior stillbirth have a two-fold higher risk of recurrence (aOR 1.96, 95% CI 1.07–3.60) compared to women with a live birth in their first pregnancy. The highest risk of recurrence occurred in the group of women with a stillbirth in early gestation between 22 and 28 weeks of gestation (a OR 2.25, 95% CI 0.62–8.15), while after 32 weeks the risk decreased. The risk of neonatal death after 34 weeks of gestation is higher in women with a history of stillbirth (aOR 6.48, 95% CI 2.61–16.1) and the risk of neonatal death increases with expectant obstetric management (aOR 10.0, 95% CI 2.43–41.1). Conclusions A history of stillbirth remains an important risk for recurrent stillbirth especially in early gestation (22–28 weeks). Women with a previous stillbirth should be counselled for elective induction in the subsequent pregnancy at 37–38 weeks of gestation to decrease the risk of perinatal death.