Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study

Modest reduction in adverse birth outcomes following the COVID-19 lockdown

Renal sarcoidosis (RS) is a rare but potentially severe manifestation of sarcoidosis, primarily affecting the kidneys through granulomatous interstitial nephritis (GIN) and calcium metabolic disturbances. This study evaluates the clinicopathological features and renal outcomes of biopsy-proven RS, focusing on identifying predictors of renal recovery and disease progression. This retrospective study included 43 biopsy-proven RS at Mayo Clinic (2012-2024). Demographic, clinical, laboratory, and histopathological data were analyzed. Renal recovery within six months was classified as complete, partial, or no recovery based on serum creatinine (sCr) changes. Long-term adverse composite outcomes included the chronic kidney disease (CKD) onset, CKD progression, end-stage kidney disease, dialysis initiation, or death. Logistic regression and Cox proportional hazards regression were used to assess predictors of renal outcomes. Among cohort, 84% exhibited interstitial nephritis, with GIN in 33%. Calcium phosphate deposits were found in 58% of cases. Hypercalciuria (90%) was more common than hypercalcemia (74%). Within six months, 86% achieved recovery (74% complete, 12% partial), while 40% experienced long-term adverse composite outcomes. Higher sCr at biopsy (≥ 2.4 mg/dL) and moderate-to-severe interstitial fibrosis and tubular atrophy (IFTA) were associated with reduced complete recovery and worse long-term outcomes; while pre-existing CKD significantly increased the risk of adverse long-term outcomes. Steroid therapy significantly increased the likelihood of complete recovery and reduced the risk of adverse long-term outcomes. Pre-existing CKD, elevated sCr at biopsy, IFTA, and steroid therapy are key predictors of renal outcomes in RS. Early diagnosis and intervention are crucial to preventing irreversible kidney damage.

PurposeNasal polyps (NPs) develop in 20% to 30% of patients with chronic rhinosinusitis. Severe forms of chronic rhinosinusitis with nasal polyposis (CRSwNP) may be treated with systemic corticosteroids (SCSs), which increase the risk for adverse clinical outcomes. This study compared the incidence of SCS-related adverse outcomes and health care resource utilization and costs between patients with CRSwNP who had SCS exposure and those who did not have SCS exposure. MethodsThis retrospective cohort study used health care claims data from adult patients with CRSwNP identified in the IBMⓇ MarketScanⓇ Databases between January 2003 and June 2019. The first SCS prescription date in SCS users or a matched date in SCS nonusers (controls) represented the index date. Enrollment for ≥1 year before and after the index date was required. SCS-related adverse outcomes and costs were compared between all SCS users and controls, and among subgroups of patients who had claims for 1–3 and ≥4 SCS prescriptions in the 12-month postindex period. Comparisons were also made among SCS users and controls who previously had and did not have NP surgery, and those with and without comorbid asthma. Inverse probability of treatment weights was applied to all comparisons, which were evaluated for a variable-length follow-up period. FindingsSCS users (n = 37,740) had a greater risk for any adverse outcome than controls (n = 7032) (incidence rate ratio [IRR] = 1.10; 95% CI, 1.05–1.16). The risk for adverse outcomes was highest in the subgroups that did not have NP surgery and that had ≥4 SCS claims (n = 2993) versus controls who did not have NP surgery (n = 5078) (IRR = 1.30; 95% CI, 1.18–1.44). Similarly, patients with asthma and ≥4 SCS claims (n = 4195) had a greater risk for SCS-related outcomes versus controls with asthma (n = 1226) (IRR = 1.36; 95% CI, 1.19–1.55). SCS users incurred 60% higher all-cause costs versus non-SCS users (P < 0.001). ImplicationsIn patients with CRSwNP, SCS use was associated with a higher risk for adverse outcomes and with increased health care costs compared with controls without SCS exposure. Alternative treatment strategies that avoid and/or reduce SCS use may decrease health care costs and the risk for adverse outcomes among patients with CRSwNP.

The influence of hours worked prior to delivery on maternal and neonatal outcomes: a retrospective cohort study

Does polycystic ovary syndrome (PCOS) confer an independent risk for adverse delivery and neonatal outcomes, based on analysis of the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database? After controlling for all potential confounding effects, women with PCOS are at an increased risk of experiencing preterm pre-labour rupture of membranes (PPROM), pre-term delivery (PTD), placental abruption, caesarean section (C/S) delivery, chorioamnionitis and post-partum maternal infections. PCOS may be associated with an increased risk of adverse perinatal outcomes. However, there remain significant gaps in understanding the correlation between PCOS and important delivery and neonatal complications. This is a retrospective population-based cohort study utilising data from the HCUP-NIS over 11 years from 2004 to 2014. A cohort of all deliveries between 2004 and 2014 inclusively was created. Within this group, all deliveries to women with PCOS were identified as part of the study group (n = 14882), and the remaining deliveries were categorised as non-PCOS births and comprised the reference group (n = 9081906). The HCUP-NIS is the largest inpatient sample database in the USA and it is comprised of hospital inpatient stays throughout the entire country. It provides information relating to 7 million inpatient stays per year, includes ∼20% of admissions, and represents over 96% of the American population. After adjustment for all potential confounders, women with PCOS were more likely to experience PPROM (aOR 1.48, 95% CI 1.20-1.83), PTD (aOR 1.37 95% CI 1.24-1.53) and placental abruption (aOR 1.63, 95% CI 1.30-2.05) and were more likely to deliver by C/S (aOR 1.50, 95% CI 1.40-1.61 (all P < 0.001). Women with PCOS more often developed chorioamnionitis (aOR 1.58, 95% CI 1.34-1.86, P < 0.001) and maternal infections (aOR 1.58, 95% CI 1.36-1.84 (both P < 0.001)). With the exception of multiple gestations (aOR 1.27, 95% CI 1.01-1.62, P = 0.04), there was no difference in the number of women who gave birth to small for gestational age (SGA) infants (aOR 0.97, 95% CI 0.82-1.15, P = 0.72) between the women with PCOS and the reference group. Intrauterine foetal deaths (IUFDs) were also comparable between the two groups (aOR 1.03, 95% CI 0.68-1.59, P = 0.88). However, congenital anomalies were more likely to occur in the offspring of women with PCOS (aOR 1.89, 95% CI 1.51-2.38, P < 0.001). This is a retrospective analysis utilising an administrative database which relies on the accuracy and consistency of the individuals coding the data. There are known limitations in how accurately hospital coding is able to capture perinatal conditions and complications, making it difficult to know with certainty that such events are accurate. Women with PCOS are more likely to experience adverse delivery and neonatal outcomes. It is important to additionally consider the risk of all other co-existing conditions frequently encountered in PCOS women, as these risks are additive and place women with PCOS at significantly increased risk of adverse pregnancy outcomes. No specific funding was obtained for this study. The authors have no conflicts of interest to disclose.

Stroke represents a prominent global health issue, exhibiting the third highest incidence of disability and a significant burden on both healthcare and the economy. Stress hyperglycemia, an acute reaction of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to adverse outcomes and mortality. Several previous studies have indicated that stress hyperglycemia, as evaluated by the stress hyperglycemia ratio (SHR), significantly increases the risk of adverse outcomes and mortality in stroke patients. However, there is a lack of further investigation into the influence of dynamic changes in stress hyperglycemia on the clinical outcomes of acute ischemic stroke (AIS) patients. Consequently, we performed a meticulous analysis, considering dose-response relationships from existing studies, to ascertain the correlation between dynamic changes in stress hyperglycemia and the susceptibility to adverse outcomes in patients with AIS. This investigation was prospectively registered in PROSPERO and adhered to the PRISMA guidelines. A comprehensive search was performed across English and Chinese databases. A two-sided random-effects model was employed to consolidate the odds ratios (ORs) of the highest vs. lowest categories of SHR. Restricted cubic spline (RCS) models were employed to estimate potential non-linear trends between SHR and the risk of adverse outcomes in AIS patients. Egger's test was utilized to assess publication bias. Heterogeneity was evaluated using Cochran's Q-test. The Newcastle-Ottawa Scale (NOS) tool was employed to evaluate the risk of bias of the included studies. The final analysis incorporated a total of thirteen studies, which were published between 2019 and 2023, encompassing a participant cohort of 184,179 individuals. The SHR exhibited a significant association with the risk of various adverse outcomes. Specifically, a higher SHR was correlated with a 2.64-fold increased risk of 3-month poor functional outcomes (OR: 2.64, 95% CI 2.05-3.41, I2 = 52.3%, P < 0.001), a 3.11-fold increased risk of 3-month mortality (OR: 3.11, 95% CI 2.10-4.59, I2 = 38.6%, P < 0.001), a 2.80-fold increased risk of 1-year mortality (OR: 2.80, 95% CI 1.81-4.31, I2 = 88%, P < 0.001), a 3.90-fold increased risk of intracerebral hemorrhage (ICH) and 4.57-fold increased risk of symptomatic ICH (sICH) (ICH-OR: 3.90, 95% CI 1.52-10.02, I2 = 84.3%, P = 0.005; sICH-OR: 4.57, 95% CI 2.05-10.10, I2 = 47.3%, P < 0.001), a 1.73-fold increased risk of neurological deficits (OR: 1.73, 95 CI 1.44-2.08, I2 = 0%, P < 0.001), and a 2.84-fold increased risk of stroke recurrence (OR: 2.84, 95 CI 1.48-5.45, I2 = 50.3%, P = 0.002). It is noteworthy that, except for hemorrhagic transformation (HT) and stroke recurrence, the remaining adverse outcomes exhibited a "J-shaped" non-linear dose-response relationship. In summary, our findings collectively suggest that increased exposure to elevated SHR is robustly linked to a heightened risk of adverse outcomes and mortality in individuals with AIS, exhibiting a non-linear dose-response relationship. These results underscore the significance of SHR as a predictive factor for stroke prognosis. Therefore, further investigations are warranted to explore the role of SHR in relation to adverse outcomes in stroke patients from diverse ethnic populations. Furthermore, there is a need to explore the potential benefits of stress hyperglycemia control in alleviating the physical health burdens associated with AIS. Maintaining a lower SHR level may potentially reduce the risk of adverse stroke outcomes. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023424852.

ABSTRACTObjectiveTo evaluate the use of twin vs singleton growth charts for detecting small‐for‐gestational‐age (SGA) twins at risk of adverse neonatal outcomes.MethodsMEDLINE, EMBASE, CINAHL, Cochrane and Scopus databases were searched electronically from inception to May 2024. The primary outcome of this meta‐analysis was the risk of composite adverse neonatal outcome in SGA fetuses in a twin pregnancy diagnosed using twin or singleton charts. The secondary outcomes included: neonatal intensive care unit (NICU) admission, oxygen supplementation or continuous positive airway pressure, mechanical ventilation, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis and neonatal mortality. Prospective and retrospective studies on neonatal outcomes of monochorionic or diamniotic twins diagnosed with SGA using both singleton and twin charts based on estimated fetal weight or birth weight were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale for cohort studies. Random‐effects head‐to‐head meta‐analyses were used to analyze the data.ResultsSix studies were included in the systematic review and five studies, including 10 554 twin pregnancies, were included in the meta‐analysis. The risk of composite adverse neonatal outcome (OR, 3.11 (95% CI, 1.83–5.26)) and that of most secondary outcomes was significantly higher in SGA fetuses diagnosed using twin charts compared with those diagnosed using singleton charts. Conversely, the risk of composite adverse neonatal outcome (OR, 1.22 (95% CI, 0.73–2.04)) and most secondary outcomes was similar when comparing SGA fetuses diagnosed using singleton charts vs non‐SGA fetuses diagnosed using twin charts, except for the risk of NICU admission, which was significantly higher in SGA fetuses diagnosed using singleton charts. When comparing non‐SGA fetuses diagnosed using twin charts vs non‐SGA fetuses diagnosed using singleton charts, the risk of composite adverse neonatal outcome was significantly lower when using twin charts (OR, 0.90 (95% CI, 0.83–0.97)). Finally, when comparing SGA vs non‐SGA fetuses diagnosed using singleton charts, there was no significant difference for the primary or secondary outcomes, except for a higher risk of NICU admission in the SGA group (OR, 1.54 (95% CI, 1.11–2.12)). Twin charts had lower sensitivity than singleton charts in predicting adverse neonatal outcome (14% (95% CI, 7–26%) vs 32% (95% CI, 24–41%)), but higher specificity (95% (95% CI, 86–98%) vs 71% (95% CI, 63–77%)).ConclusionsTwin charts increase the specificity but reduce the sensitivity for the detection of SGA compared with singleton charts. Nevertheless, twin charts detect cases at higher risk of adverse neonatal outcome, which may be the cases that require intervention. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

BackgroundAlthough treatment decisions for localized prostate cancer (LPC) are preference-sensitive, the extent to which individuals with LPC receive preference-concordant treatment is unclear. In a sample of individuals with LPC, the purpose of this study was to (a) assess concordance between the influence of potential adverse treatment outcomes and treatment choice; (b) determine whether receipt of a decision aid predicts higher odds of concordance; and (c) identify predictors of concordance from a set of participant characteristics and influential personal factors.MethodsParticipants reported the influence of potential adverse treatment outcomes and personal factors on treatment decisions at baseline. Preference-concordant treatment was defined as (a) any treatment if risk of adverse outcomes did not have a lot of influence, (b) active surveillance if risk of adverse outcomes had a lot of influence, or (c) radical prostatectomy or active surveillance if risk of adverse bowel outcomes had a lot of influence and risk of other adverse outcomes did not have a lot of influence. Data were analyzed using descriptive statistics and logistic regression.ResultsOf 224 participants, 137 (61%) pursued treatment concordant with preferences related to adverse treatment outcomes. Receipt of a decision aid did not predict higher odds of concordance. Low tumor risk and age ≥ 60 years predicted higher odds of concordance, while attributing a lot of influence to the impact of treatment on recreation predicted lower odds of concordance.ConclusionsRisk of potential adverse treatment outcomes may not be the foremost consideration of some patients with LPC. Assessment of the relative importance of patients’ stated values and preferences is warranted in the setting of LPC treatment decision making.Clinical trial registration: NCT01844999 (www.clinicaltrials.gov).

Renal involvement is the major factor determining the long-term outcome of children with Henoch-Schonlein Purpura (HSP) nephritis. The precise incidence of adverse outcomes is debatable; moreover, there are conflicting data on the validity of prognostic factors for predicting adverse outcome in children with HSP nephritis. Difficulties in prognostication are compounded by lack of non-invasive diagnostic methods in children suspected of having HSP. The purpose of this article is to review recent data evaluating the role of serum galactose-deficient IgA in the pathogenesis of HSP nephritis and its potential role as a non-invasive diagnostic tool. Recent studies evaluating the role of prognostic markers and the risk of adverse long-term outcomes in children with HSP nephritis are also described. HSP nephritis, although relatively benign in most children, can lead to significant chronic kidney disease in a subset of children, especially on very longterm follow-up. Health-care providers need to be aware of this and tailor appropriate follow-up and screening tests to identify early signs of renal functional deterioration, so that therapies that can retard the rate of progression can be instituted early.

Update on Childhood Urinary Tract Infections and Reflux

Is maternal polycystic ovary syndrome (PCOS) associated with increased risks for a broad spectrum of psychiatric and mild neurodevelopmental disorders in offspring? Maternal PCOS and/or anovulatory infertility is independently, and jointly with maternal obesity, perinatal problems, cesarean delivery and gestational diabetes, associated with increased risks in offspring for almost all groups of psychiatric and mild neurodevelopmental disorders with onset in childhood or adolescence. Maternal PCOS was previously associated with autism spectrum disorder, attention-deficit/hyperactivity disorders and possibly developmental delay in offspring. Few studies have investigated the association between maternal PCOS and other psychiatric and neurodevelopmental disorders in offspring. This was a population-based cohort study in Finland including all live births between 1996 and 2014 (n = 1 105 997). After excluding births to mothers with symptoms similar to PCOS, a total of 1 097 753 births by 590 939 mothers remained. Children were followed up until 31 December 2018, i.e. up to the age of 22 years. National registries were used to link data of the included births and their mothers. Data from 24 682 (2.2%) children born to mothers with PCOS were compared with 1 073 071 (97.8%) children born to mothers without PCOS. Cox proportional hazards modeling was used to evaluate the hazard ratio (HR) and 95% CI for the risk of neuropsychiatric disorders in relation to maternal PCOS. Stratified analyses were performed to test the independent role of PCOS and the joint effects of PCOS with maternal obesity, perinatal problems, cesarean delivery, gestational diabetes and use of fertility treatment. The analysis was adjusted for maternal age, country of birth, marriage status at birth, smoking, parity, psychiatric disorders, prescription of psychotropic N05/N06 during pregnancy and systemic inflammatory diseases when applicable. A total of 105 409 (9.8%) children were diagnosed with a neurodevelopmental or psychiatric disorder. Firstly, maternal PCOS was associated with any psychiatric diagnosis (HR 1.32; 95% CI 1.27-1.38) in offspring. Particularly, the risk was increased for sleeping disorders (HR 1.46; 95% CI 1.27-1.67), attention-deficit/hyperactivity disorders and conduct disorders (HR 1.42; 95% CI 1.33-1.52), tic disorders (HR 1.42; 95% CI 1.21-1.68), intellectual disabilities (HR 1.41; 95% CI 1.24-1.60), autism spectrum disorder(HR 1.40; 95% CI 1.26-1.57), specific developmental disorders (HR 1.37; 95% CI 1.30-1.43), eating disorders (HR 1.36; 95% CI 1.15-1.61), anxiety disorders (HR 1.33; 95% CI 1.26-1.41), mood disorders (HR 1.27; 95% CI 1.18-1.35) and other behavioral and emotional disorders (ICD-10 F98, HR 1.49; 95% CI 1.39-1.59). In short, there was no significant difference between sexes. The results were robust when restricting the analyses to the first-born children or births to mothers without psychiatric diagnosis or purchase of psychotropic medication. Secondly, stratified analysis according to maternal BMI showed that the risk of any neuropsychiatric disorder was increased in offspring to normal-weight mothers with PCOS (HR 1.20; 95% CI 1.09-1.32), and markedly higher in those to severely obese mothers with PCOS (HR 2.11; 95% CI 1.76-2.53) compared to offspring to normal-weight mothers without PCOS. When excluding perinatal problems, mothers with PCOS were still associated with increased risks of any neuropsychiatric disorders in offspring (HR 1.28; 95% CI 1.22-1.34) compared to mothers without PCOS. However, an additional increase was observed for PCOS in combination with perinatal problems (HR 1.99; 95% CI 1.84-2.16). Likewise, excluding cases with maternal gestational diabetes (HR 1.30; 95% CI 1.25-1.36), cesarean delivery (HR 1.29; 95% CI 1.23-1.35) or fertility treatment (HR 1.31; 95% CI 1.25-1.36) did not eliminate the associations. The register-based prevalence of PCOS was lower than previously reported, suggesting that this study may capture the most severe cases. To combine anovulatory infertility with PCOS diagnosis as PCOS exposure might introduce diagnostic bias. It was not feasible to distinguish between subtypes of PCOS. Furthermore, familial factors might confound the association between maternal PCOS and neuropsychiatric disorders in offspring. Maternal BMI was available for birth cohort 2004-2014 only and there was no information on gestational weight gain. This study provides further evidence that maternal PCOS and/or anovulatory infertility, independently and jointly with maternal obesity, perinatal problems, gestational diabetes and cesarean delivery, implies a broad range of adverse effects on offspring neurodevelopment. These findings may potentially help in counseling and managing pregnancies. This study was supported by the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C and C.L.), THL Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. was supported by the China Scholarship Council during her training in Karolinska Institute. L.K. was supported by the China Scholarship Council for his PhD study in Karolinska Institute. The authors have no competing interests to disclose. N/A.

In a prospective cohort study, we evaluated the effect of Helicobacter pylori seropositivity on the risk of future adverse cardiovascular outcomes among patients with acute coronary syndrome (ACS). In 433 patients, IgA and IgG antibodies to H pylori, along with classic risk factors, including hypertension, diabetes, hyperlipidaemia, smoking and family history of coronary artery disease (CAD) were determined. Short and long-term follow-up information on adverse outcomes, defined as recurrence of unstable angina, myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, and sudden cardiac death was obtained. None of the classic CAD risk factors correlated with incidence of either short- or long-term outcomes. Seropositivity for H pylori was significantly associated with risk of short-term adverse outcomes, and independently predicted their incidence in multivariate regression (R = 3.05, p < 0.001). Results failed to show such an association between H pylori seropositivity and long-term adverse outcomes. H pylori infection may affect short-term prognosis in patients with ACS. Randomised trials are needed to evaluate the role of H pylori eradication in these patients.

Fetal growth restriction (FGR) as a common pregnancy complication is generally defined as the failure of a fetus to achieve its genetically determined full growth potential due to placental dysfunction. Early-onset (<32. gestational week) FGR is associated strongly with abnormal trophoblastic invasion and consequent placental insufficiency. Conditions leading to FGR are the disorders inherent to the fetal-placental-maternal unit, fetal malnutrition, resulting in a significantly increased risk of stillbirth, neonatal morbidity, neonatal death, and long-term adverse outcome. Once the fetal size, typically using estimated fetal weight and/or abdominal circumference below the tenth percentile compared to gestational age reference standards, multimodality assessment (including Doppler velocimetry in umbilical, and middle cerebral arteries, CTG and biophysical profile) is recommended. At present, the most recognized criteria to define early and late FGR are those derived from an international Delphi survey consensus. Early diagnosis, close follow-up and timely delivery of pregnancies with FGR are of crucial importance for perinatal short- and long-term outcome. The main distinction between small for gestational age (SGA) and growth-restricted fetus is that the healthy SGA fetus may be small but not at increased risk of adverse perinatal outcome. Orv Hetil. 2025; 166(9): 331–340.

Is embryo vitrification associated with a higher risk of adverse perinatal outcomes than slow-freezing? Embryo vitrification was not associated with increased risks of adverse perinatal outcomes of pre-term birth (PTB), low birthweight (LBW), small for gestational age (SGA), large for gestational age (LGA) and macrosomia, as compared to slow-freezing. Vitrification is becoming a widely adopted technology for embryo cryopreservation with higher embryo survival rate and live birth rate than the slow-freezing technique. However, limited data are currently available on risks of adverse perinatal outcomes following vitrification as compared to that of slow-freezing. The impact of vitrification on perinatal outcomes remains further to be elucidated. Six large reproductive medical centers in Guangdong province, Southeast of China, took part in this multicenter retrospective cohort study. Cohorts of 3199 live born singletons after Day 3 frozen-thawed embryo transfer (FET) cycles with either vitrification or slow-freezing between January 2011 and December 2015 were included in the study. Each patient only contributed one cycle per cohort and vanishing twins were excluded. Propensity score (PS) matching was used to control for potential confounding factors. All live-born singletons following either a vitrified or a slow-frozen cleavage FET cycle during the period from 2011 to 2015 were analyzed. Perinatal outcomes of PTB, LBW, macrosomia, SGA and LGA were compared. The vitrified and slow-frozen cohorts were matched by propensity scores with a 1:1 ratio accounting for potential confounding factors associated with perinatal outcomes. These variables included baseline demographics (maternal age, BMI, education level, parity, type of infertility and cause of infertility), as well as IVF characteristics (insemination method, endometrial preparation protocol and embryo cryopreservation duration). A total of 2858 cases from vitrified embryo transfer (ET) and 341 babies from the slow-freezing group were included. After PS matching, 297 pairs of newborns were generated for comparison. The median gestational age was 39weeks for both cohorts and the birthweights were comparable (3187.7 ± 502.1g in the vitrified group vs. 3224.6 ± 483.6 in the slow-freezing group, P>0.05). There were no significant differences between the two groups on the incidence of PTB (5.4% vs. 7.7%), LBW (6.7% vs. 5.7%), macrosomia (5.7% vs. 6.1%), SGA (12.5% vs. 8.4%) and LGA (6.4% vs. 8.1%). Parallel logistic regression analysis indicated that vitrification was non-inferior to slow-freezing method in terms of the occurrence of PTB (OR, 0.68 [95% CI, 0.35, 1.31]), LBW (OR, 1.19[0.61-2.32]), macrosomia (OR, 0.94 [0.48-1.86]), SGA (1.55[0.91-2.64]) and LGA (0.78[0.42-1.45]), P>0.05. Sex-stratified PS matching models with multivariable regression analysis further confirmed that vitrification did not increase the risks of above-mentioned adverse perinatal outcomes in either the male or female infant cohort. Although the analysis was adjusted for a number of important confounders, the hospital dataset did not contain other potential confounders such as the medical history and obstetrics outcomes of women during pregnancy to allow adjustment. In addition, the current findings are only applicable to cleavage stage FET, but not pronuclei stage or blastocyst stage ET. Vitrified ET, in comparison with slow-frozen ET, was not associated with increased risks of adverse neonatal outcomes. With its superiority on live birth rates and non-inferiority on safety perinatal outcomes, transition from slow-freezing to the use of vitrification for embryo cryopreservation is reassuring. Nonetheless, future research is needed for the long-term effects of vitrification method on offspring's health outcomes. The study was funded by the National Key Research and Development Program (2016YFC100205), Guangzhou Science and Technology Project (201804020087), Guangdong Province Science and Technology Project (2016A020218008) and Guangdong Provincial Key Laboratory of Reproductive Medicine (2012A061400003). The authors have no conflicts of interest to declare.

Background Previous studies have found a relationship between overall systemic lupus erythematosus (SLE) activity and adverse pregnancy outcomes. We sought to investigate whether 5 types of specific types of SLE activity either in the 6 months prior to conception or during pregnancy were related to adverse pregnancy outcome. Materials and methods 149 pregnancies occurred in 114 women with mean age 23.7 (SD 6.8) years at SLE diagnosis and 31.0 (SD 5.3) at conception. 68% were White, 15% Hispanic, 11% Black, 7% Asian. Seven women had a history of antiphospholipid syndrome and 23 had a prior adverse pregnancy outcome. During the study period, 40 (27%) pregnancies had an adverse outcome. Cytopenias (15%) and nephritis (11%) were the most common types of SLE activity during pregnancy. In univariable analyses, nephritis 6 months before conception (OR 7.3, 95% CI: [1.5, 35.2]) and during pregnancy OR 4.4 (1.3–14.9) and cytopenias during pregnancy (OR 4.8 [1.7, 14.0]) were significantly associated with adverse outcome. Hispanic ethnicity, prior adverse pregnancy outcome, and steroid and/or azathioprine use during pregnancy were also associated with adverse outcome. In multivariable analyses, nephritis (OR 3.5 [1.0–12.2]), cytopenias (OR 4.2 [1.4,12.2]) and serositis (OR 5.7 [1.1–30.3]) during pregnancy were associated with adverse outcome (Table 1) Results 149 pregnancies occurred in 114 women with mean age 23.7 (SD 6.8) years at SLE diagnosis and 31.0 (SD 5.3) at conception. 68% were White, 15% Hispanic, 11% Black, 7% Asian. Seven women had a history of antiphospholipid syndrome and 23 had a prior adverse pregnancy outcome. During the study period, 40 (27%) pregnancies had an adverse outcome. Cytopenias (15%) and nephritis (11%) were the most common types of SLE activity during pregnancy. In univariable analyses, nephritis 6 months before conception (OR 7.3, 95% CI: [1.5, 35.2]) and during pregnancy OR 4.4 (1.3–14.9) and cytopenias during pregnancy (OR 4.8 [1.7, 14.0]) were significantly associated with adverse outcome. Hispanic ethnicity, prior adverse pregnancy outcome, and steroid and/or azathioprine use during pregnancy were also associated with adverse outcome. In multivariable analyses, nephritis (OR 3.5 [1.0–12.2]), cytopenias (OR 4.2 [1.4,12.2]) and serositis (OR 5.7 [1.1–30.3]) during pregnancy were associated with adverse outcome (Table 1). Conclusions The majority of pregnancy outcomes were favourable in this SLE cohort. After adjusting for ethnicity, prior adverse pregnancy outcomes, and medications during pregnancy, nephritis, cytopenias and serositis disorders during pregnancy were associated with an elevated risk of adverse pregnancy outcome. Prior studies have suggested variable impact of lupus nephritis on pregnancy outcomes, but this study uniquely demonstrates an additional association between cytopenias and serositis during pregnancy and adverse pregnancy outcomes.