Healthy lifestyle mitigates the impact of low-level air pollution on adverse pregnancy outcomes: Evidence from a population-based study.

Factors Influencing Adverse Perinatal Outcomes in Pregnancies Achieved Through Use of Assisted Reproductive Technology (ART)

ABSTRACTObjectiveTo quantify the association between a combination of modifiable prepregnancy lifestyle factors and the risk of adverse pregnancy outcomes (APOs).DesignProspective cohort study.SettingThe Japan Environment and Children's Study.PopulationA total of 79 703 pregnant Japanese women without chronic disease.MethodsMaternal lifestyle before pregnancy was assessed using a self‐administered questionnaire. A healthy lifestyle score (HLS, 0–5 points) was calculated based on adherence to five prepregnancy healthy lifestyle factors: healthy weight, high‐quality diet, regular physical activity, not smoking, and not drinking alcohol. Relative risks (RRs) and 95% credible intervals (CrIs) were estimated using a Bayesian log‐binomial regression model.Main Outcome MeasuresComposite APOs, defined as the development of any APO, including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, and small‐for‐gestational‐age, transcribed from medical records.ResultsA total of 13 894 women (17.4%) experienced one or more APOs. HLS was inversely associated with the risk of APOs in a dose–response manner. Women with an HLS of 5 points had a 33% (RR 0.67; 95% CrI, 0.61–0.74) lower risk of APOs than those with the lowest HLS (0–1 points). The population attributable fraction of five healthy lifestyle factors was 10.3%. A 1‐point increase of HLS could have reduced APO cases by 6.6%.ConclusionsA higher HLS was associated with a lower risk of APOs, suggesting that adopting a healthy lifestyle before pregnancy may reduce the risk of APOs, which can increase the risk of future chronic diseases in both mother and child.

Background: Genetic factors increase the risk of depression, but the extent to which this can be offset by lifestyle factors is unknown. In the present study, we investigated whether a healthy lifestyle is associated with lower risk of depression regardless of genetic risk. Methods: Data for this prospective analysis were obtained from the UK Biobank and consisted of 339,944 participants (37-73 years old) without depression between 2006 and 2010. Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2-4), or high (quintile 5) according to polygenic risk scores for depression. Healthy lifestyle scores — including no current smoking, regular physical activity, a healthy diet, and a body mass index < 30 kg/m2 — was categorized into favorable, intermediate, and unfavorable lifestyles. Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) of the associations of genetic risk and lifestyle factors with depression. Finding: During a median follow-up of 8.1 years (2,723,692 person-years), 5,749 incidences of depression were ascertained. The risk of depression was 25% higher among those at high genetic risk compared with those at low genetic risk (HR = 1.25, 95% CI: 1.15-1.36). Unfavorable lifestyle was associated with a 70% increased risk of depression compared with that of a favorable lifestyle (HR = 1.70, 95% CI: 1.57-1.84). Of the participants with a high genetic risk and unfavorable lifestyle, 2.75% (95% CI, 2.36%-3.19%) developed depression compared with 1.25% (95% CI: 1.15%-1.36%) of participants with low genetic risk and a favorable lifestyle (HR = 2.06, 95% CI: 1.74-2.45). There was no significant interaction between genetic risk and healthy lifestyle (P for interaction = 0.75). Among participants at high genetic risk, a favorable lifestyle was associated with a 40% lower relative risk of depression than an unfavorable lifestyle (HR = 0.60, 95% CI: 0.51-0.72). Interpretation: Genetic and combined lifestyle factors were independently associated with the incidence of depression. Hence, our findings suggest that a healthy lifestyle may lower the risk of depression across different genetic risk categories, emphasizing the benefit of adherence to a healthy lifestyle independent of genetic risk. Funding Statement: National Natural Science Foundation of China (91746205, 71910107004, 71673199). Declaration of Interests: The authors declare that they have no conflicts of interests. Ethics Approval Statement: Not required.

Prolonged time to pregnancy is associated with a greater risk of adverse outcomes

Pregnancies complicated by late-onset fetal growth restriction (FGR) are at increased risk of short- and long-term morbidities. Despite this, identification of cases at higher risk of adverse perinatal outcome, at the time of FGR diagnosis, is challenging. The aims of this study were to elucidate the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, and to determine their predictive accuracy. This was a prospective study of consecutive singleton pregnancies complicated by late-onset FGR. Late-onset FGR was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 3rd centile, or EFW or AC < 10th centile and umbilical artery (UA) pulsatility index (PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile, diagnosed after 32 weeks. EFW, uterine artery PI, UA-PI, fetal middle cerebral artery (MCA) PI, CPR and umbilical vein blood flow normalized for fetal abdominal circumference (UVBF/AC) were recorded at the time of the diagnosis of FGR. Doppler variables were expressed as Z-scores for gestational age. Composite adverse perinatal outcome was defined as the occurrence of at least one of emergency Cesarean section for fetal distress, 5-min Apgar score < 7, umbilical artery pH < 7.10 and neonatal admission to the special care unit. Logistic regression analysis was used to elucidate the strength of association between different ultrasound parameters and composite adverse perinatal outcome, and receiver-operating-characteristics (ROC)-curve analysis was used to determine their predictive accuracy. In total, 243 consecutive singleton pregnancies complicated by late-onset FGR were included. Composite adverse perinatal outcome occurred in 32.5% (95% CI, 26.7-38.8%) of cases. In pregnancies with composite adverse perinatal outcome, compared with those without, mean uterine artery PI Z-score (2.23 ± 1.34 vs 1.88 ± 0.89, P = 0.02) was higher, while Z-scores of UVBF/AC (-1.93 ± 0.88 vs -0.89 ± 0.94, P ≤ 0.0001), MCA-PI (-1.56 ± 0.93 vs -1.22 ± 0.84, P = 0.004) and CPR (-1.89 ± 1.12 vs -1.44 ± 1.02, P = 0.002) were lower. On multivariable logistic regression analysis, Z-scores of mean uterine artery PI (P = 0.04), CPR (P = 0.002) and UVBF/AC (P = 0.001) were associated independently with composite adverse perinatal outcome. UVBF/AC Z-score had an area under the ROC curve (AUC) of 0.723 (95% CI, 0.64-0.80) for composite adverse perinatal outcome, demonstrating better accuracy than that of mean uterine artery PI Z-score (AUC, 0.593; 95% CI, 0.50-0.69) and CPR Z-score (AUC, 0.615; 95% CI, 0.52-0.71). A multiparametric prediction model including Z-scores of MCA-PI, uterine artery PI and UVBF/AC had an AUC of 0.745 (95% CI, 0.66-0.83) for the prediction of composite adverse perinatal outcome. While CPR and uterine artery PI assessed at the time of diagnosis are associated independently with composite adverse perinatal outcome in pregnancies complicated by late-onset FGR, their diagnostic performance for composite adverse perinatal outcome is low. UVBF/AC showed better accuracy for prediction of composite adverse perinatal outcome, although its usefulness in clinical practice as a standalone predictor of adverse pregnancy outcome requires further research. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Maternal adherence to healthy lifestyle behaviors during pregnancy has been associated with reduced risk of obesity in the offspring. Our objective is to examine associations between a composite healthy lifestyle score (HLS) in expectant mothers and adverse offspring birth outcomes and childhood obesity. The Lifeways Study comprises 665 mother-child pairs. A composite HLS (scored 0-5) based on high dietary quality (top 40% of the Healthy Eating Index (HEI)-2015), moderate to vigorous physical activity (MVPA), healthy pre-pregnancy BMI (18.5-24.9 kg/m2), never smoker, and no/moderate alcohol intake was calculated. Birth outcomes were abstracted from hospital records. Offspring waist circumference (WC) and BMI was determined at age 5 and 9. Logistic regression tested HLS associations with offspring outcomes. Offspring birth weight, length, and head circumference were positively associated with the maternal HLS (p < 0.001), whereas child BMI and incidence of overweight/obesity at age 5 and 9 were negatively associated (p < 0.05). In multivariable models, a lower maternal HLS was associated with increased risk of low birth weight (LBW) (P trend = 0.04) and lower likelihood of macrosomia (P trend = 0.03). Examined individually, poor maternal dietary quality, smoking, and alcohol intake were associated with higher risk of LBW (p < 0.04). Likelihood of macrosomia and combined overweight/obesity at age 5 and 9 years were greater among mothers with a pre-pregnancy BMI in the range with obesity (p < 0.04). Smoking during pregnancy was also linked to greater risk of childhood overweight/obesity (OR:1.91, 95% CI:1.01-3.61, p = 0.04 at age 5 and OR: 2.14, 95% CI:1.01-4.11, p = 0.03 at age 9). Our findings suggest that maternal adherence to a healthy lifestyle during pregnancy, in particular having a good quality diet, not smoking, and no/low alcohol intake in combination with a healthy pre-pregnancy BMI, is associated with reduced risk of adverse offspring birth outcomes and childhood obesity.

To investigate the association of healthy lifestyle factors before pregnancy (body mass index [BMI] 18.5-24.9, nonsmoking, 150 min/wk or more of moderate-to-vigorous physical activity, healthy eating [top 40% of Dietary Approaches to Stop Hypertension score], no or low-to-moderate alcohol intake [less than 15 g/d], and use of multivitamins) with risk of adverse pregnancy outcomes. We conducted a secondary analysis of prospectively collected data for women without chronic diseases who are participating in an ongoing cohort in the United States (the NHSII [Nurses' Health Study II]). Healthy lifestyle factors preceding pregnancy were prospectively assessed every 2-4 years from 1991 to 2009 with validated measures. Reproductive history was self-reported in 2001 and 2009. A composite outcome of adverse pregnancy outcomes that included miscarriage, ectopic pregnancy, gestational diabetes, gestational hypertension, preeclampsia, preterm birth, stillbirth, or low birth weight was assessed. Overall, 15,509 women with 27,135 pregnancies were included. The mean maternal age was 35.1±4.2 years. Approximately one in three pregnancies (n=9,702, 35.8%) was complicated by one or more adverse pregnancy outcomes. The combination of six low-risk factors was inversely associated with risk of adverse pregnancy outcomes in a dose-dependent manner ( P for trend <.001). Compared with women who had zero or one healthy lifestyle factor, those with six had a 37% lower risk of adverse pregnancy outcomes (relative risk 0.63, 95% CI 0.55-0.72), driven primarily by lower risks of gestational diabetes, gestational hypertension, and low birth weight. All prepregnancy healthy lifestyle factors, except avoiding harmful alcohol consumption and regular physical activity, were independently associated with lower risk of adverse pregnancy outcomes after mutual adjustment for each other. Healthy BMI, high-quality diet, and multivitamin supplementation showed the strongest inverse associations with adverse pregnancy outcomes. If the observed relationships were causal, 19% of adverse pregnancy outcomes could have been prevented by the adoption of all six healthy lifestyle factors (population attributable risk 19%, 95% CI 13-26%). Prepregnancy healthy lifestyle is associated with a substantially lower risk of adverse pregnancy outcomes and could be an effective intervention for the prevention of adverse pregnancy outcomes.

Risk of adverse pregnancy outcomes and impact of statin use in pregnant women with familial hypercholesterolemia.

Lifestyle factors and fetal and childhood origins of type 2 diabetes: a prospective study of Chinese and European adults

Major trauma in pregnancy: prediction of maternal and perinatal adverse outcomes

Objective: To explore the association between the consumption of chemical fertilizers and the risk of low birth weight (LBW), to provide references for prevention programs on LBW and to improve the birth outcomes. Methods: Stratified multivariate logistic regression method was used in this study involving 153 preterm LBW infants, 179 term LBW infants and 204 normal control infants that were randomly selected from the birth monitoring data between October 2007 and September 2012 in Pingding county, Shanxi province. Associations between the risk of LBW and maternal exposure to chemical fertilizers during pregnancy were identified. A normal control group was set up to compare results between preterm and term LBW groups. Results: Totally, 18 749 infants were born between 2007 and 2012, with the total incidence rates of LBW as 48.5‰, preterm LBW as 19.4‰, and term LBW as 29.1‰. Concerning the case control study on preterm LBW, after adjustment for confounding factors, the risk of preterm LBW appeared 2.51 (95%CI: 1.05-5.99) times higher in villages with annual consumption of chemical fertilizer ≥100 tons than those villages that using chemical fertilizer less than 50 tons. No significant statistical associations were found between the amounts of household chemical fertilizer consumption and the risks of preterm LBW. Regarding the case control study on term LBW, after adjustment for confounding factors, in villages with ≥100 tons annual consumption of chemical fertilizers, the risk of term LBW was 4.03 (95%CI: 1.63-9.92) times of the risk in villages where the annal use of chemical fertilizers was less than 50 tons. There was no significant association between household consumption of chemical fertilizers and the risk of term LBW. Conclusions: Maternal exposure to chemical fertilizers during pregnancy was associated with the risk of LBW. Our findings suggested that the amount of chemical fertilizer consumption in rural areas seemed also associated with the risks of other adverse pregnancy outcomes. Women should avoid the chance of exposure to chemical fertilizers during pregnancy and the consumption of chemical fertilizers should be carefully managed.

Background: A healthy lifestyle is associated with a lower risk of premature death. Metabolic pathways of a healthy lifestyle and their association with mortality remain to be understood. This study aimed to identify the metabolomic profile of a healthy lifestyle score and examine its prospective association with all-cause and cause-specific mortality, including death from cardiovascular disease (CVD) and cancer. Methods: The population included 12,146 participants from the Nurses’ Health Study (NHS), NHS II and Health Professionals Follow-Up Study (HPFS)(83% women, 97% white, aged 55±9y). Plasma metabolites were profiled using high-throughput liquid chromatography mass-spectrometry at baseline (NHS:1989-1990; NHSII:1996-1999; HPFS:1993-1995). The healthy lifestyle score was computed by summing the total number of healthy lifestyle factors participants adhered to from validated questionnaires at baseline: healthy diet (Alternative Healthy Eating Index, upper 40%), moderate alcohol intake (women: 5-15 g/d; men: 5-30 g/d), moderate-to-vigorous physical activity (≥30min/d), never smoking and normal BMI (18.5-24.9kg/m 2 ). Deaths were ascertained with death certificates and medical records. The metabolite profile was identified using elastic net regressions with train test validation split (70-30%). Metabolic pathways were determined using Metabolite Set Enrichment Analysis (MSEA). Multivariable-adjusted Cox proportional hazards regressions were used to estimate hazard ratios and 95% confidence intervals (HR[CI]) per unit of score of the healthy lifestyle metabolite profile with mortality risk. Results: The identified profile included 88 metabolites and correlated with the healthy lifestyle score (Pearson r=0.43-0.44; p&lt;0.001). Triglyceride and diglyceride metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were directly associated (p&lt;0.001). Among individual lifestyle factors, the profile was most strongly correlated with normal BMI (r pb =0.43; p&lt;0.001). Over 32y of follow-up, there were 3,851 deaths, including 749 deaths from CVD and 994 from cancer. Participants with a higher healthy lifestyle metabolite profile score had lower risk of all-cause (HR=0.79[0.73, 0.85]) and CVD mortality (HR=0.77[0.58, 0.95]), but not cancer (HR=0.91[0.77, 1.05]). Significant associations persisted after further adjustment for the healthy lifestyle score. Conclusions: In US adults, we identified a metabolite profile related to a healthy lifestyle largely reflecting lipid metabolism pathways. A higher metabolite score was associated with lower subsequent all-cause mortality risk, specifically from CVD. Findings provide novel insights into potential metabolic pathways underlying the association between a healthy lifestyle and lower premature mortality.

BackgroundAntiphospholipid syndrome (APS) is a major immune-related disorder that leads to adverse pregnancy outcomes (APO), including recurrent miscarriage, placental abruption, preterm birth, and fetal growth restriction. Antiphospholipid antibodies (aPLs), particularly anticardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2GP1), and lupus anticoagulant (LA), are considered key biomarkers for APS and are closely associated with adverse pregnancy outcomes. This is a prospective observational cohort study to use machine learning model to predict adverse pregnancy outcomes in APS patients using early pregnancy aPL levels and clinical features.MethodsThis prospective study began data collection and follow-up for APS patients undergoing pregnancy monitoring in January 2023, and all data collection and follow-up were completed by January 2025. The samples were divided into the APO group and non-APO group. Multivariable logistic regression and ridge regression were used to identify independent predictive factors for adverse pregnancy outcomes. Six machine learning models were developed: Light Gradient Boosting Machine (LGBM), CatBoost, Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Random Forest (RF), and Multi-Layer Perceptron (MLP). The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, and F1 score. The best-performing model was further explained using Shapley Additive Explanations (SHAP) analysis. Additionally, decision curve analysis (DCA) was performed to assess the clinical utility of the models.ResultsA total of 708 patients were included. Ridge regression analysis identified aβ2GP1, LA1/LA2, aCL, gestational week at termination, age at first miscarriage, age, BMI during pregnancy, use of medication, >3 adverse pregnancies, 1–2 adverse pregnancies, preeclampsia, and natural miscarriage as significant predictors. Among the six models, the XGBoost model performed the best for predicting adverse pregnancy outcomes (AUROC = 0.864). Decision curve analysis (DCA) further confirmed the superiority of the XGBoost model, and feature importance analysis revealed that aβ2GP1 levels were the most important variable among the 12 factors.ConclusionThis study demonstrated that the XGBoost model, integrating aPL levels and clinical features, offers an effective approach to predicting adverse pregnancy outcomes in APS patients. The model enables clinicians to quickly and accurately identify high-risk pregnancies, providing valuable support for personalized clinical interventions and treatments.

Maternal adherence to healthy lifestyle behaviours during pregnancy has been associated with reduced risk of obesity in the offspring. Our objective is to examine the association between a composite healthy lifestyle score (HLS) derived from body mass index (BMI), dietary quality, physical activity, smoking and alcohol intake, in expectant mothers and adverse offspring birth outcomes and childhood obesity. The Lifeways Cross-Generation Study comprises 1082 mother-child pairs. We defined five healthy lifestyle factors during pregnancy including: high dietary quality (top 40% of the Healthy Eating Index (HEI)-2015), moderate to vigorous physical activity (MVPA), healthy pre-pregnancy BMI (18.5–24.9 Kg/m2), never smoker, and no/moderate alcohol intake. A composite HLS was calculated (scored 0–5). Birthweight, length and head circumference were abstracted from hospital records. Waist circumference and BMI was determined when the child was 5 and 9 years. Logistic regression analyses were used to test HLS and individual HLS component associations with offspring birth and childhood outcomes. Offspring birthweight, length and head circumference were positively associated with the number of maternal healthy lifestyle factors (p &lt; 0.001), whereas child BMI and incidence of overweight/obesity at age 5 and 9 were negatively associated with the maternal HLS (p &lt; 0.05). In multivariable models, a lower maternal HLS (0–2 healthy lifestyle factors) was associated with increased risk of low birthweight (LBW) (OR:1.17, 95% CI:1.01–2.69, p = 0.043) and lower likelihood of macrosomia (OR:0.73, 95% CI:0.24–0.99, p = 0.034), relative to those with 5 healthy lifestyle factors. Examination of the individual HLS components revealed that, poor maternal dietary quality, smoking and alcohol intake were associated with higher risk of LBW (OR:1.61, 95%CI:1.01–7.85, p = 0.043, OR: 2.54, 95%CI:1.26–5.12, p = 0.025 and OR:2.30, 95%CI:1.01–5.26, p = 0.031, respectively). Likelihood of macrosomia and combined overweight/obesity at age 5 and 9 years was greater among mothers with a pre-pregnancy BMI in the obese range (OR:2.18, 95%CI:1.23–3.85, p = 0.042, OR:2.19, 95%CI:1.01–5.08, p = 0.03 and OR:3.89, 95%CI:1.00–10.59, p = 0.04, respectively). Smoking during pregnancy was also linked to greater risk of childhood overweight/obesity (OR:1.91, 95%CI:1.01–3.61, p = 0.04 at age 5 and OR:2.14, 95%CI:1.01–4.11, p = 0.03 at age 9). Our findings suggest that maternal adherence to a healthy lifestyle during pregnancy, in particular having a good quality diet, not smoking and no/low alcohol intake in combination with a healthy pre-pregnancy BMI, is associated with reduced risk of adverse offspring birth outcomes and childhood obesity. These findings highlight the potential benefits of implementing maternal based multifactorial interventions to improve offspring birth outcomes and combat childhood adiposity.

SummaryBackgroundEarlier studies have proposed a link between the Interpregnancy Interval (IPI) and unfavorable birth outcomes. However, it remains unclear if the outcomes of previous births could affect this relationship. We aimed to investigate whether the occurrence of adverse outcomes–small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW)–at the immediately preceding pregnancy could alter the association between IPI and the same outcomes at the subsequent pregnancy.MethodsWe used a population-based linked cohort from Brazil (2001–2015). IPI was measured as the difference, in months, between the preceding birth and subsequent conception. Outcomes included SGA (<10th birthweight percentile for gestational age and sex), LBW (<2500 g), and PTB (gestational age <37 weeks). We calculated risk ratios (RRs), using the IPI of 18–22 months as the reference IPI category, we also stratified by the number of adverse birth outcomes at the preceding pregnancy.FindingsAmong 4,788,279 births from 3,804,152 mothers, absolute risks for subsequent SGA, PTB, and LBW were higher for women with more adverse outcomes in the preceding delivery. The RR of SGA and LBW for IPIs <6 months were greater for women without previous adverse outcomes (SGA: 1.44 [95% Confidence Interval (CI): 1.41–1.46]; LBW: 1.49 [1.45–1.52]) compared to those with three previous adverse outcomes (SGA: 1.20 [1.10–1.29]; LBW: 1.24 [1.15–1.33]). IPIs ≥120 months were associated with greater increases in risk for LBW and PTB among women without previous birth outcomes (LBW: 1.59; [1.53–1.65]; PTB: 2.45 [2.39–2.52]) compared to women with three adverse outcomes at the index birth (LBW: 0.92 [0.78–1.06]; PTB: 1.66 [1.44–1.88]).InterpretationOur study suggests that women with prior adverse outcomes may have higher risks for adverse birth outcomes in subsequent pregnancies. However, risk changes due to differences in IPI length seem to have a lesser impact compared to women without a prior event. Considering maternal obstetric history is essential in birth spacing counseling.Funding10.13039/100010269Wellcome Trust225925/Z/22/Z.