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Background The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. Methods and findings A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. Conclusions In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. Trial registration The trial is registered with ISRCTN (41918550)., Author(s): Maryam de Brun 1, Anders Magnuson 2, Scott Montgomery 2,3,4, Snehal Patil 2, David Simmons 5,6, Kerstin Berntorp 7, Stefan Jansson 8, Ulla-Britt Wennerholm 9, Anna-Karin Wikström 10, Helen [...]

Objective: To investigate whether perineal wound complications in the first birth, alone or in conjunction with obstetric anal sphincter injury (OASI), is associated with an increased risk of OASI in the second birth. Design: Nationwide population‐based cohort study. Setting: Sweden. Population: Women (n = 411 317) with first and second singleton vaginal births in Sweden, 2001–2019. Methods: Data on diagnostic codes and surgical procedures were retrieved from the Swedish Medical Birth Register and the Swedish Patient Register. A perineal wound complication was defined as wound infection, dehiscence or perineal haematoma within 2 months of childbirth. Main outcome measures: Associations between wound complications in the first birth and OASI in the second birth were investigated with logistic regression and presented as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs). Results: In total, 2619 (0.6%) women had a wound complication in the first birth, and 5318 (1.3%) had an OASI in the second birth. Women with a wound complication but no OASI in the first birth had more than doubled odds of OASI in the second birth (aOR 2.73, 95% CI 2.11–3.53). Women with OASI and a wound complication in the first birth had almost tenfold odds (aOR 9.97, 95% CI 6.53–15.24) of recurrent OASI. Conclusions: Perineal wound complication in the first birth increases the likelihood of OASI in a subsequent birth. [ABSTRACT FROM AUTHOR]

BACKGROUND Preeclampsia in a first pregnancy is a strong risk factor for preeclampsia in a second pregnancy. Whether chronic hypertension developed after a first pregnancy (interpregnancy hypertension) affects the recurrence risk of preeclampsia is unknown. METHODS This is a population-based cohort study of 391,645 women with their first and second singleton births between 2006 and 2017. Exposure groups were women with preeclampsia in their first pregnancy, interpregnancy hypertension, or both risk factors. Women with neither risk factor were used as a reference group. We calculated the adjusted relative risk (aRR) with 95% confidence intervals (CIs) for overall preeclampsia in the second pregnancy as well as preterm (<37 gestational weeks) and term (≥37 gestational weeks) subgroups of the disease. RESULTS Women with preeclampsia in their first pregnancy who did or did not develop interpregnancy hypertension had rates of preeclampsia in their second pregnancy of 21.5% and 13.6%, respectively. In the same population, the corresponding rates of preterm preeclampsia were 5.5% and 2.6%, respectively. After adjusting for maternal factors, women with preeclampsia in their first pregnancy who developed interpregnancy hypertension and those who did not have almost the same risk of overall preeclampsia in their second pregnancy (aRRs with 95% CIs: 14.51; 11.77–17.89 and 12.83; 12.09–13.62, respectively). However, preeclampsia in the first pregnancy and interpregnancy hypertension had a synergistic interaction on the outcome of preterm preeclampsia (aRR with 95% CI 26.66; 17.44–40.80). CONCLUSIONS Women with previous preeclampsia who developed interpregnancy hypertension had a very high rate of preterm preeclampsia in a second pregnancy, and the two risk factors had a synergistic interaction. [ABSTRACT FROM AUTHOR]

Objective: To explore whether the association between polycystic ovary syndrome (PCOS) and pre‐eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre‐eclampsia. Design: Nationwide register‐based cohort study. Setting: Sweden. Population: Nulliparous women with PCOS (n = 22 947) and non‐PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997–2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti‐androgenic drugs during 2005–2017 (n = 2301 among PCOS women). Methods: The risk of pre‐eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors. Main outcome measures: Overall pre‐eclampsia. Early/late (delivery <34/≥34 weeks) pre‐eclampsia. Pre‐eclampsia with or without a small‐for‐gestational‐age (SGA) infant. Results: Compared with controls, women with PCOS had a 29% increased risk of pre‐eclampsia (predictor adjusted OR 1.29, 95% CI 1.20–1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre‐eclampsia seemed stronger than its association with late pre‐eclampsia (predictor adjusted OR 1.64 (95% CI 1.33–2.02) and 1.26 (95% CI 1.17–1.37). Additionally, the association seemed slightly stronger between PCOS and pre‐eclampsia in women with an SGA infant than without. Conclusions: Women with PCOS face an increased risk for pre‐eclampsia, especially early pre‐eclampsia and pre‐eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre‐eclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up. Material and methods: Study participants were identified in the population‐based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid‐pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow‐up visit 4–15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up. ClinicalTrials.gov registration NCT05693285. Results: In the screening phase, fibrinogen, cadherin‐5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D‐binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow‐up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up. Conclusions: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid‐pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Severe perineal lacerations (SPLs), common worldwide, are associated with short- and long-term complications: pelvic floor disorders, fecal incontinence, fistula, and profound psychological impacts. Limited research suggests that experiencing SPL may influence future reproductive intentions, but research on outcomes is lacking. Methods: We analyzed the effect of experiencing SPL during a first delivery among a large cohort of Swedish births between 1992 and 2013. We used linear and multinomial logistic regression to estimate the associations between SPL and four reproductive outcomes: subsequent total birth number, probability of a second birth, interpregnancy interval (IPI), and subsequent scheduled cesarean birth. Results: Among 947,035 singleton live-born first-births, we found that experiencing SPL was associated with slightly fewer overall births in fully adjusted models (a decrease of −0.020 births; 95% confidence interval [CI]: −0.028 to −0.012), but no difference in the probability of a second birth (risk ratio [RR]: 1.00; 95% CI: 0.99 to 1.00) or IPI. Scheduled cesarean was increased in births after SPL (adjusted RR: 4.57; 95% CI: 4.42 to 4.73). A secondary comparison of SPL to severe postpartum hemorrhage suggests that some of these observed differences may be related to experiencing any severe outcome, and some specifically to perineum disruption. Conclusion: This study provides a deeper understanding of the long-term impacts of SPL, which may be useful in informing best clinical practices for supporting women who have experienced SPL. [ABSTRACT FROM AUTHOR]

Background and Purpose: Few large‐scale studies examine whether maternal myasthenia gravis (MG) is a risk factor for complications during pregnancy and childbirth. This study evaluated whether maternal MG is associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. Methods: We conducted a nationwide Swedish register‐based cohort study of women who gave birth to singleton infants (≥22 gestational weeks) during 1987–2019. Exposed women were diagnosed with MG before or during the index pregnancy (N = 443). Unexposed women comprised 4249 women without a diagnosis of MG, matched for age, parity, hospital, and year of childbirth. The risks of adverse pregnancy, delivery, and neonatal outcomes for women with MG were estimated using regression modeling and presented as adjusted odds ratios (aOR). Results: There was no increased risk of pregnancy complications in women with MG. Women with MG had a spontaneous onset of labor less often than women without MG (69.8% vs. 79.5%; aOR 0.59; p < 0.001) as well as higher labor induction rates and elective cesarean section deliveries (16.0% vs. 12.3%, aOR 1.42; p = 0.02 and 12.0% vs. 8.1%, aOR 1.59; p = 0.009). Infants of women with MG were born on average 2 days earlier (p = 0.002); however, these infants did not have a higher risk of having low APGAR, being small for gestational age, or having a congenital malformation. Conclusion: This first nationwide study of pregnancy in women with MG in Sweden demonstrates reassuring results overall, suggesting generally safe pregnancy outcomes for women with MG and their infants. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether mild neonatal hypoxic ischaemic encephalopathy (HIE) in term born infants is associated with cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. Design: Population‐based cohort study. Setting: Sweden, 2009–2015. Population: Live term born infants without congenital malformations or chromosomal abnormalities (n = 505 075). Methods: Birth and health data were retrieved from Swedish national health and quality registers. Mild HIE was identified by diagnosis in either the Swedish Medical Birth Register or the Swedish Neonatal Quality Register. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Main outcome measures: A composite of the outcomes cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. Results: Median follow‐up time was 3.3 years after birth. Of 414 infants diagnosed with mild HIE, 17 were classified according to the composite outcome and incidence rates were 12.6 and 2.9 per 1000 child‐years in infants with and without HIE respectively. Infants with mild HIE was four times as likely to be diagnosed with the composite outcome (HR 4.42, 95% CI 2.75–7.12) compared with infants without HIE. When analysed separately, associations were found with cerebral palsy (HR 21.50, 95% CI 9.59–48.19) and death (HR 19.10, 95% CI 7.90–46.21). HRs remained essentially unchanged after adjustment for covariates. Conclusions: Mild neonatal HIE was associated with neurological morbidity and mortality in childhood. Challenges include identifying infants who may develop morbidity and how to prevent adverse outcomes. Linked article: This article is commented on by William M. Curtin, pp. 1610 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.17596. [ABSTRACT FROM AUTHOR]

Background The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject. Methods and findings We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age ( From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] -57/10,000 [95% CI -106/10,000 to -8/10,000], I.sup.2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one ( Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD -127/10,000, [95% CI -204/10,000 to -50/10,000], I.sup.2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI -29/10,000 to 84/10,000], I.sup.2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited. Conclusions In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174, Author(s): Mårten Alkmark 1,2,*, Judit K. J. Keulen 3, Joep C. Kortekaas 4, Christina Bergh 5,6, Jeroen van Dillen 4, Ruben G. Duijnhoven 3, Henrik Hagberg 1,2, Ben Willem Mol [...]

Introduction: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy. Material and methods: First‐trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific. Results: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518–0.588) * PlGFRoche –1.112 (95% CI −2.773 to 0.550); r = 0.966, mean difference −24.6 (95% CI −26.4 to −22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618–0.729) * PlGFThermoFisher –0.199 (95% CI −2.292 to 1.894); r = 0.945, mean difference −13.8 (95% CI −15.1 to −12.6). PlGFRoche = 1.809 (95% CI 1.694–1.923) * PlGFPerkinElmer +2.010 (95% CI −0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8–26.4). PlGFRoche = 1.237 (95% CI 1.113–1.361) * PlGFThermoFisher +0.840 (95% CI −3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4–12.1). PlGFThermoFisher = 1.485 (95% CI 1.363–1.607) * PlGFPerkinElmer +0.296 (95% CI −2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6–15.1). PlGFThermoFisher = 0.808 (95% CI 0.726–0.891) * PlGFRoche –0.679 (95% CI −4.456 to 3.099); r = 0.937, mean difference −10.8 (95% CI −12.1 to −9.4). Conclusion: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first‐trimester prediction models for preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: Investigate associations between pre‐pregnancy participation and performance in a demanding cross‐country ski race (proxy for exercise volume and fitness) and perinatal outcomes. Pre‐registered protocol: osf.io/aywg2. Design: Prospective cohort study. Setting: Based on entire overlap between the Vasaloppet registry and the population‐based Swedish Pregnancy Register. Sample All female Vasaloppet participants 1991–2017 with subsequent singleton delivery (skiers), and age‐ and county‐matched non‐skiers. Methods: We calculated odds ratios (ORs) for non‐skiers versus skiers (model 1) and, among skiers, by performance (model 2), in Bayesian logistic regressions adjusted for socio‐demographics, lifestyle factors, and comorbidities. We repeated calculations adjusting for early pregnancy body mass index (potential mediator) and explored robustness (selection/exposure settings; multiple comparisons correction). Main outcome measures: Twenty‐nine important perinatal outcomes, predefined based on existing expert consensus. Results: Non‐skiers (n = 194 384) versus skiers (n = 15 377) (and slower versus faster performance, not shown) consistently had higher odds of gestational diabetes mellitus (GDM) (OR 1.70, 95% highest density interval: 1.40–2.09), excessive gestational weight gain (GWG) (1.28, 1.22–1.38), psychiatric morbidity (1.60, 1.49–1.72), any caesarean section (CS) (1.34, 1.28–1.40), elective CS (1.39, 1.29–1.49), and large‐for‐gestational‐age babies (>90th percentile, 1.11, 1.04–1.18); lower odds of inadequate GWG (0.83, 0.79–0.88); and no associations with fetal/neonatal complications (e.g. preterm birth [1.09, 0.98–1.20], small for gestational age [SGA] [1.23, 1.05–1.45]). Adjustment for body mass index attenuated associations with excessive (1.20, 1.14–1.30) and inadequate GWG (0.87, 0.83–0.92) and large for gestational age (1.07, 1.00–1.13). Conclusion: Non‐skiers compared with skiers, and slower versus faster performance, consistently displayed higher odds of GDM, excessive GWG, psychiatric morbidity, CS and large‐for‐gestational‐age babies; and lower odds of inadequate GWG, after adjustment for socio‐demographic and lifestyle factors and comorbidities. There were no associations with fetal/neonatal complications. [ABSTRACT FROM AUTHOR]

Preeclampsia is a maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation associated with multisystemic complications, including brain alterations. Indeed, brain complications associated with preeclampsia are the leading direct causes of fetal and maternal morbidity and mortality, especially in low- and middle-income countries. In addition to the well-recognized long-term adverse cardiovascular effects of preeclampsia, women who have had preeclampsia have higher risk of stroke, dementia, intracerebral white matter lesions, epilepsy, and perhaps also cognitive decline postpartum. Furthermore, increasing evidence has also associated preeclampsia with similar cognitive and cerebral disorders in the offspring. However, the mechanistic links between these associations remain unresolved. This article summarizes the current knowledge about the cerebrovascular complications elicited by preeclampsia and the potential pathophysiological mechanisms involved, emphasizing the impaired brain vascular function in the mother and their offspring. [ABSTRACT FROM AUTHOR]

Background: More than two in five Swedish women are overweight or obese when becoming pregnant. Maternal overweight or obesity and excessive pregnancy weight gain are associated with several adverse pregnancy outcomes. The underlying mechanisms that link maternal adiposity, diet, exercise, pregnancy weight gain with pregnancy outcome are incompletely understood. Methods: We describe the design for a cross-sectional study of pregnant women at Uppsala University Hospital, Sweden. All participants delivered by elective cesarean section before the onset of labor. At inclusion, participants answered two questionnaires concerning their dietary and exercise habits. Fasting maternal blood samples (buffy coat, plasma, serum) were collected. During the cesarean section, biopsies of maternal subcutaneous and visceral adipose tissues were obtained. Placental tissue was collected after delivery. All biological samples were processed as soon as possible, frozen on dry ice, and stored at -70 °C. Pregnancy outcomes and supplementary maternal characteristics were collected from medical records. Results: In total, 143 women were included in the study. Of these women, 33.6% were primiparous, 46.2% had a pre-pregnancy body mass index (BMI) over 25 kg/m2, and 11.2% of the offspring were born large for gestational age (LGA). Complete collection, that is both questionnaires and all types of biological samples, was obtained from 81.1% of the participants. Conclusions: This study is expected to provide a resource for exploration of the associations between maternal weight, diet, exercise, pregnancy weight gain, and pregnancy outcome. Results from this study will be published in peer-reviewed, international scientific journals. This study was approved by the Regional Ethics Review Board in Uppsala (approval no 2014/353) and with an amendment by the Swedish Ethical Review Authority (approval no 2020-05844). [ABSTRACT FROM AUTHOR]

Introduction: Alcohol consumption during pregnancy is related to severe birth complications such as low birthweight, preterm birth and birth defects. During the last decade, the Alcohol Use Disorders Identification Test (AUDIT) has been used as a screening tool in Swedish maternal healthcare units to identify hazardous, pre‐pregnancy alcohol use. However, evaluation of the screening with AUDIT, as well as adverse maternal or neonatal outcomes, has not been assessed at a national level. Material and methods: This was a population‐based cohort study of 530 458 births from 2013 to 2018 using demographic, reproductive and maternal health data from the Swedish Pregnancy Register. Self‐reported alcohol consumption in the year before pregnancy, measured as AUDIT scores, was categorized into moderate (6–13 points) and high‐risk (14–40 points) consumption, with low‐risk (0–5 points) consumption as the reference group. Associations with pregnancy‐ and birth outcomes were explored with logistic regressions using generalized estimating equation models, adjusting for maternal and socioeconomic characteristics. Estimates are presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: High‐risk and moderate pre‐pregnancy alcohol consumption was associated with preeclampsia, preterm birth and birth of an infant small for gestational age (SGA), but these associations were nonsignificant after adjustments. Prior moderate‐risk (aOR 1.29, 95% CI 1.17–1.42) and high‐risk consumption (aOR 1.62, 95% CI 1.17–2.25) increased the likelihood of intrapartum and neonatal infections. Conclusions: Apart from identifying hazardous alcohol consumption prior to pregnancy and the offer of counseling, screening with the AUDIT in early pregnancy indicates a high risk of inflammatory‐/placenta‐mediated pregnancy and birth outcomes. For most outcomes, AUDIT was not an independent contributor when adjusting for confounding factors. Hazardous alcohol use prior to pregnancy was independently linked to intrapartum and neonatal infections; conditions associated with morbidity and long‐term sequalae. These associations may be explained by alcohol‐induced changes in the maternal or fetal immune system in early pregnancy or persistent alcohol intake during pregnancy, or may depend on unidentified confounding factors. [ABSTRACT FROM AUTHOR]

This document is a response to a letter regarding a study on the association between serum myasthenia gravis (MG) and adverse pregnancy, delivery, and neonatal outcomes. The authors address the concerns raised in the letter and clarify their methodology. They explain that they used a directed acyclic graph (DAG) to guide their selection of confounders and followed STROBE guidelines. They also discuss the distinction between etiological research and prediction research, and state that their study aimed to investigate causal associations. The authors agree that maternal use of MG medications may influence neonatal outcomes, but note that this was not the focus of their research. They conclude by acknowledging the importance of medication use and stating that their next paper will explore this topic in more detail. [Extracted from the article]