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We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy. PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023. Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included. We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using R and Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach. Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01–3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07–4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65–6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0–1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46–7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01–8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68–3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88–8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20–4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82–3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81–3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13–0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63–4.70) in subsequent pregnancies. Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: It is unclear whether women with psoriasis who receive adequate management or achieve better control of their psoriasis before and during pregnancy could eliminate the negative effects. Objectives: The objective of this study was to investigate the association between physician visits for psoriasis and adverse pregnancy outcomes. Methods: This study used the National Health Insurance database and Birth Certificate Application in Taiwan. This research further categorized the study subjects into mothers with mild/severe psoriasis who visited physicians for psoriasis before delivery, mothers with mild/severe psoriasis who did not visit a physician for psoriasis before delivery, and mothers without psoriasis. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the occurrence of adverse pregnancy outcomes, including maternal and neonatal outcomes. Results: 3,339 mothers with severe psoriasis, 41,296 mothers with mild psoriasis, and 2,017,271 mothers without psoriasis were included in this study. The mothers with mild/severe psoriasis demonstrated a significantly higher risk of labor complications and maternal risk factors. After adjusting for confounders, mothers with severe psoriasis who did not visit a physician for psoriasis demonstrated significantly higher odds of labor complications (OR: 1.217), maternal risk factors (OR: 1.507), having low‑birth weight infants (OR: 1.236), etc., than mothers without psoriasis. Conclusion: This study demonstrated that mothers with psoriasis had a higher risk of adverse pregnancy outcomes. In addition, seeking medical care for psoriasis, particularly for women with severe psoriasis, appeared to exert a protective effect against adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Placental histopathologic lesions are dichotomized into "present" or "absent" and have limited inter-rater reliability. Continuous metrics are needed to characterize placental health and function. Tissue sections (N = 64) of human placenta were stained with CD34 antibody and hematoxylin. Proportion of the villous space occupied by fetal vascular endothelium (%FVE; pixels positive for CD34/total pixels) was evaluated for effect sizes associated with pregnancy outcomes, smoking status, and subtypes of lesions (n = 30). Time to fixation>60 min significantly increased the quantification. Large effect sizes were found between %FVE and both preterm birth and intrauterine growth restriction. These results demonstrate proof-of-concept for this vascular estimation. • Novel quantification of fetal vascular development may relate to pregnancy outcomes. • Lower vascularization may be present in cases of adverse fetal outcomes. • Quantification complements traditional histopathology. [ABSTRACT FROM AUTHOR]

Background: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the un derstudied association between neighborhood- level socioeconomic position during early pregnancy and the risk of gastroschisis, an abdominal birth defect of increasing prevalence. Methods: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997-2011). To characterize neighborhood-level socioeconomic position, we conducted a principal component analysis to construct two indices--Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputations for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence. Results: Mothers residing in moderate (NDI Tertile 2 aOR = 1.23; 95% CI = 1.03, 1.48 and nSEPI Tertile 2 aOR = 1.24; 95% CI = 1.04, 1.49) or low socioeconomic neighborhoods (NDI Tertile 3 aOR = 1.28; 95% CI = 1.05, 1.55 and nSEPI Tertile 3 aOR = 1.32, 95% CI = 1.09, 1.61) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods. Conclusions: Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis. [ABSTRACT FROM AUTHOR]

Objective: To quantify the absolute risks of adverse fetal outcomes and maternal mortality following nonobstetric abdominopelvic surgery in pregnancy. Summary Background Data: Surgery is often necessary in pregnancy, but absolute measures of risk required to guide perioperative management are lacking. Methods: We systematically searched MEDLINE, EMBASE, and EvidenceBased Medicine Reviews from January 1, 2000, to December 9, 2020, for observational studies and randomized trials of pregnant patients undergoing nonobstetric abdominopelvic surgery. We determined the pooled proportions of fetal loss, preterm birth, and maternal mortality using a generalized linear random/mixed effects model with a logit link. Results: We identified 114 observational studies (52 [46%] appendectomy, 34 [30%] adnexal, 8 [7%] cholecystectomy, 20 [17%] mixed types) reporting on 67,111 pregnant patients. Overall pooled proportions of fetal loss, preterm birth, and maternal mortality were 2.8% (95% CI 2.2-3.6), 9.7% (95% CI 8.3-11.4), and 0.04% (95% CI 0.02-0.09; 4/10,000), respectively. Rates of fetal loss and preterm birth were higher for pelvic inflammatory conditions (eg, appendectomy, adnexal torsion) than for abdominal or nonurgent conditions (eg, cholecystectomy, adnexal mass). Surgery in the second and third trimesters was associated with lower rates of fetal loss (0.1%) and higher rates of preterm birth (13.5%) than surgery in the first and second trimesters (fetal loss 2.9%, preterm birth 5.6%). Conclusions: Absolute risks of adverse fetal outcomes after nonobstetric abdom- inopelvic surgery vary with gestational age, indication, and acuity. Pooled estimates derived here identify high-risk clinical scenarios, and can inform implementation of mitigation strategies and improve preoperative counselling. [ABSTRACT FROM AUTHOR]

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention. [Display omitted] The bidirectional relationship between cardiovascular prevention and maternal-fetal dyad. Life's Essential 8, along with mental health and socio-economic factors are crucial players in pre-gestational CV health (left-sided picture). An inadeguate maternal cardio-metabolic health represents a trigger for the development of pregnancy-related complications, which, in turn, further worsen maternal cardio-metabolic health. Maternal cardio-metabolic environment and pregnancy-related complications negatively affect fetal developmental programming (center). These conditions are strongly associated with increased risk of short- and long-term CV event and cardio-metabolic issues, both for the mother and her offspring (right-sided picture). [ABSTRACT FROM AUTHOR]

Introduction: Placental vascular disease, characterized by Maternal Vascular Malperfusion (MVM) lesions, is considered to be the underlying cause of pregnancy complications. Aim is to evaluate the relationship between the cumulative number of MVM lesion types, and adverse pregnancy- and neonatal outcomes.Methods: This retrospective cohort study included 272 women with singleton gestations who gave birth at a Dutch tertiary hospital between 2017 and 2018 with available placental histopathology reports. Analyzed according to the Amsterdam Placental Workshop Group Consensus Statement, placentas were divided into groups based on the cumulative number of MVM lesions: no lesions (n = 124), 1-2 types (n = 124) and 3-5 types of lesions (n = 24).Results: The proportion of placenta syndrome (PS) was highest (95.8%) in the 3-5 MVM lesions group (p < 0.001). The presence of MVM lesions was highly associated with PS during pregnancy (aOR 6.81, 95% CI 3.76-12.33). Furthermore, every additional type of MVM lesion corresponded with a threefold increased odds for the occurrence of PS (aOR 3.00, 95% CI 2.10-4.29). The group with 3-5 types of MVM lesions showed the highest incidence of adverse neonatal outcomes, lower mean birth weight, prolonged hospitalization, NICU admissions and neonatal deaths (aOR 6.47, 95% CI 0.33-127.68), corresponding with a fourfold increased odds for the occurrence of neonatal death for every additional MVM lesion (aOR 4.19, 95% CI 1.39-12.68).Discussion: A higher number of MVM lesion types is strongly associated with an increased incidence of adverse pregnancy- and neonatal outcomes, indicating that guidelines should focus also on the amount of MVM lesion types for the monitoring/management of subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To investigate pregnancy outcomes and the effects of pregnancy on kidney function in patients with stage 3-5 chronic kidney disease (CKD).Methods: This was a retrospective study. The clinical data of women with pregnancies complicated by stage 3-5 CKD who delivered in the Peking University First Hospital from January 1st, 2013, to December 31st, 2020, were analyzed.Results: Fifty-three patients with 54 pregnancies were studied. The mean levels of serum creatinine and eGFR in the first trimester were 138.4 ± 76.7 μmol/l and 44.9 ± 13.5 ml/min/1.73 m2, respectively. The perinatal mortality rate was 1.92%. The mean gestational age at birth was 35.4 weeks, and the average infant birth weight was 2333 g. The average gestational week at delivery of patients with stage 3a CKD was 36.8 ± 2.1 weeks and there were no adverse neonatal outcomes. Compared with that in early pregnancy, the mean eGFR at 6 months after delivery decreased (52.3 ± 7.3 vs 44.8 ± 10.5 ml/min per 1.73 m2, P < 0.01) in patients with stage 3a CKD and urine protein ≥ 1 g/24 h and in patients with stage 3b CKD and urine protein ≥ 1 g/24 h (38.0 ± 2.7 vs. 26.9 ± 10.1 ml/min per 1.73 m2, P = 0.03).Conclusion: The pregnancy outcomes of patients with stage 3a CKD and proteinuria<1 g/24 h are acceptable. Pregnancy accelerates renal function deterioration more significantly among patients with stage 3-5 CKD and urinary protein concentrations above 1 g/24 h. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between aspirin use during first pregnancy and later maternal cardiovascular risk.Study Design: In this secondary analysis of a prospective cohort, we included participants who carried their first pregnancy to 20 + weeks, had data regarding aspirin use, and attended a study visit 2-7 years following delivery. The exposure was aspirin use during the first pregnancy. We calculated aspirin use propensity scores from logistic regression models including baseline variables associated with aspirin use in pregnancy and cardiovascular risk. Outcomes of interest were incident cardiovascular-related diagnoses 2-7 years following delivery. Robust Poisson regression calculated the risk of outcomes by aspirin exposure, adjusting for the aspirin use propensity score.Main Outcome Measures: The primary outcome was a composite of incident cardiovascular diagnoses at the time of the study visit: cardiovascular events, chronic hypertension, metabolic syndrome, prediabetes or type 2 diabetes, dyslipidemia, and chronic kidney disease.Results: Of 4,480 women included, 84 (1.9%) reported taking aspirin during their first pregnancy. 52.6% of participants in the aspirin-exposed group and 43.0% in the unexposed group had the primary outcome. After adjusting for the aspirin use propensity scores, aspirin use during the first pregnancy was not associated with any of the outcomes.Conclusion: We did not detect an association between aspirin use during the first pregnancy and cardiovascular-related diagnoses 2-7 years later. Our study was only powered to detect a large difference in relative risk, so we cannot rule out a smaller difference that may be clinically meaningful. [ABSTRACT FROM AUTHOR]

Cardiomyopathy (CDM) in pregnancy is associated with maternal morbidity and mortality. To explore trends and clinical outcomes in CDM subtypes during delivery hospitalizations. We used the National Inpatient Sample database to identify delivery hospitalizations between 2005-2020 by CDM subtypes: peripartum (PPCM), dilated (DCM), hypertrophic (HCM), and restrictive (RCM). Maternal and fetal outcomes were identified using International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes. Baseline characteristics and temporal trends of CDM subtypes were analyzed. Maternal cardiovascular, pregnancy, and fetal outcomes were evaluated by CDM subtype using univariate logistic regression. The primary outcome was in-hospital mortality. During 2005-2020, 37,125 out of 61,811,842 delivery hospitalizations were complicated by CDM. Among CDM-related delivery hospitalizations, the most prevalent were DCM (46%), followed by PPCM (45.6%), HCM (4.6%), and RCM (3.9%). The rates of in-hospital mortality (1.7%), adverse cardiovascular events such as acute heart failure (17%), cardiogenic shock (3.4%), and cardiac arrest (3.1%), and adverse pregnancy outcomes such as preeclampsia (14.2%) and preterm labor (11%), were highest among PPCM (all p < 0.0001). The prevalence of PPCM (49.1% to 38.5%) decreased while the prevalence of HCM (2.7% to 8.8%) and DCM (48% to 52.2%) increased over time. Over a 15-year period, PPCM had higher rates of in-hospital mortality, cardiovascular events, and adverse pregnancy outcomes compared to other CDM subtypes. While the prevalence of PPCM decreased over time, the prevalence of HCM and DCM increased. Hence, further research on cardiomyopathies during pregnancy and prospective studies on this vulnerable patient cohort are urgently needed. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing by cell-free DNA analysis is offered to pregnant women worldwide to screen for fetal aneuploidies. In noninvasive prenatal testing, the fetal fraction of cell-free DNA in the maternal circulation is measured as a quality control parameter. Given that fetal cell-free DNA originates from the placenta, the fetal fraction might also reflect placental health and maternal pregnancy adaptation. This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. We performed a retrospective cohort study of women with singleton pregnancies opting for noninvasive prenatal testing between June 2018 and June 2019 within the Dutch nationwide implementation study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing [TRIDENT]-2). Multivariable logistic regression analysis was used to assess associations between fetal fraction and adverse pregnancy outcomes. Fetal fraction was assessed as a continuous variable and as <10th percentile, corresponding to a fetal fraction <2.5%. The cohort comprised 56,110 pregnancies. In the analysis of fetal fraction as a continuous variable, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27 [95% confidence interval, 1.89–2.78]), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37 [1.28–1.45]) and <2.3rd percentile (adjusted odds ratio, 2.63 [1.96–3.57]), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02 [1.01–1.03]). No association was found for fetal congenital anomalies (adjusted odds ratio, 1.02 [1.00–1.04]), stillbirth (adjusted odds ratio, 1.02 [0.96–1.08]), or neonatal death (adjusted odds ratio, 1.02 [0.96–1.08]). Similar associations were found for adverse pregnancy outcomes when fetal fraction was <10th percentile. In early pregnancy, a low fetal fraction is associated with increased risk of adverse pregnancy outcomes. These findings can be used to expand the potential of noninvasive prenatal testing in the future, enabling the prediction of pregnancy complications and facilitating tailored pregnancy management through intensified monitoring or preventive measures. [Display omitted] [ABSTRACT FROM AUTHOR]

Pregnant women are a special group that is sensitive to adverse external stimuli, causing metabolic abnormalities and adverse pregnancy outcomes. Microplastics (MPs), an environmental pollutant widely used in various fields, can induce a variety of toxic responses in mammals. Recent studies verified an association between MPs and metabolic disorders. Our research built a gestational mouse model in which polystyrene microplastics (PS-MPs) of 1 μm size were consumed at concentrations of 0.1, 1, and 10 mg/L during pregnancy. Results indicated that PS-MPs induced placental malfunction and fetal growth retardation. Significant glucose disorders, decreased liver function, hepatic inflammation, and oxidative stress were also observed after PS-MPs exposure. The hepatic SIRT1/IRS1/PI3K pathway was inhibited in the 10 mg/L PS-MPs exposure group. Our study found that PS-MPs activated inflammatory response and oxidative stress by increasing hepatic lipopolysaccharide (LPS) that inhibited the hepatic SIRT1/IRS1/PI3K pathway, ultimately leading to insulin resistance, glucose metabolism disorders, and adverse pregnancy outcomes. This study provides a basis for preventing environment-related gestational diabetes and concomitant adverse pregnancy outcomes. [Display omitted] • PS-MPs have been verified to disrupt hepatic glucose metabolism during gestation. • PS-MPs caused IR by inducing hepatic inflammatory response and OS during gestation. • PS-MPs destroyed the structure of the placenta, causing FGR and intrauterine death. • SIRT1 inhibited by PS-MPs plays a role in glycometabolism and embryo implantation. [ABSTRACT FROM AUTHOR]

Background and Aims: Good glycemic control is crucial to reduce the risk of adverse pregnancy outcomes. Our aim was to evaluate the efficacy of Flash Glucose Monitoring (FGM) on glucose control in women with pregestational diabetes.Methods and Results: Forty women with inadequately controlled type 1 (T1D, n = 34) and type 2 (T2D, n = 6) diabetes at conception were randomly assigned to two arms: the Flash Glucose group (FG, n = 21) using FGM, and the control group (CG, n = 19) using self-monitoring of blood glucose (SMBG). Glycated hemoglobin (HbA1c, %), time in (TIR), below (TBR) and above (TAR) range, glucose variability as well as the occurrence of maternal and neonatal adverse outcomes, were evaluated. HbA1c decreased significantly (p < 0.01) and similarly (-0.65 ± 0.7 vs. -0.67 ± 0.8 for FG and CG, respectively; p = 0.89) in both groups during pregnancy. HbA1c reduction was positively associated with the number of daily FGM scans (p < 0.01). TBR (12.1 ± 2.0% vs. 19.6 ± 3.9%, p = 0.04) and the mean of the daily serum glucose difference (MODD) index (59.1 ± 5.4 vs. 77.7 ± 4.6, p = 0.02) were significantly lower in FG at second trimester. The rates of perinatal adverse outcomes were not different in the two studied groups.Conclusions: In women with pregestational diabetes, FGM and SMBG had similar efficacy on glucose control during pregnancy. FGM showed additional advantages in terms of TBR and glucose variability. Achievement of good metabolic results depended on the adequate use of glucose sensor.Registration: At ClinicalTrials.gov as NCT04666818 on December 14, 2020. [ABSTRACT FROM AUTHOR]

Background: Presently, the results of studies assessing the association of hypertensive disorders in pregnancy (HDP) with adverse pregnancy outcomes (APOs) in offspring remain inconclusive, and a complete overview is missing. We performed a meta-analysis of cohort studies to review and summarize the association between HDP and risk of APOs in offspring.Methods: PubMed, Embase, Web of Science and Chinese databases were searched through May 2019 to identify eligible studies. Outcomes of interest were APOs including perinatal death, fetal death, stillbirth, neonatal death, congenital malformations, preterm birth (PTB), very preterm birth (VPTB), intrauterine growth restriction (IUGR), small for gestational age (SGA), low birth weight (LBW), and very low birth weight (VLBW). Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Results: Total 152 cohort studies involving 1,426,742 mothers with HDP and 36,374,542 mothers without HDP were included for analysis. Overall, mothers with HDP compared with those without HDP had a significantly higher risk of perinatal death (OR = 2.86), fetal death (OR = 2.82), stillbirth (OR = 1.93), neonatal death (OR = 1.55), congenital malformations (OR = 2.66), IUGR (OR = 5.48), SGA (OR = 3.39), LBW (OR = 5.02), VLBW (OR = 1.74), PTB (OR = 4.20) and VPTB (OR = 3.26) in offspring. Relevant heterogeneity moderators were identified by subgroup analyses. The sensitivity analysis yielded consistent results. No evidence of publication bias was observed.Conclusion: The present study indicates that HDP significantly increases risk of APOs. Further research is needed to explore efficient management methods to minimize the risk of APOs associated with HDP. [ABSTRACT FROM AUTHOR]

There is limited robust evidence on the course of pregnancy and its outcomes in women with psoriatic arthritis (PsA) on which to base recommendations for the management of these patients. The primary objective was to review available data on (I) disease activity during pregnancy and on (II) adverse pregnancy outcomes (APO) in women with PsA. Secondly, neonatal outcomes and treatment of the rheumatic disease were investigated. Systematic literature search within the databases Pubmed and Embase until 30 Nov 2020 was performed. Additionally, reference lists of included studies and of review articles revealed by the search were screened. All full text articles identified and published in English language were systematically evaluated by two reviewers. All studies that reported on one of the primary outcomes and included at least five pregnancies in women with PsA were considered. The review of 734 search results revealed 13 eligible publications reporting on a total of 2,332 pregnancies in women with PsA. Nine studies reported on PsA activity and showed an increase or worsening of disease activity after delivery compared to the pregnancy period. APOs were reported by nine studies. Adjusted analyses of APOs did not show an increased risk for gestational diabetes, small for gestational age and low birth weight in PsA patients in relation to the respective comparator groups. However, there were signals for a higher pre-eclampsia, elective caesarean section and preterm birth risk in PsA pregnancies. Meta-analysis was not performed due to study heterogeneity. This review showed a postpartum deterioration of disease activity in women with PsA and no risk elevation for gestational diabetes, small for gestational age and low birth weight. A higher risk for pre-eclampsia, elective caesarean section and preterm birth in PsA pregnancies cannot be ruled out. Differences in the studies investigated limit overall summary statements on disease activity and APOs in women with PsA. Harmonization of study approaches, instruments and outcome reporting is crucial to ensure informed counselling of patients with PsA before, during and after pregnancy that is based on robust data. CRD42020162242. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: This study aims to estimate the incidence of adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) in Germany.Methods: Pregnant women were identified from a health claims database for the year of 2016. Three groups were defined: general population without GDM, women with GDM without treatment and women with GDM and insulin treatment. Operationalisation of outcomes was aligned with the hyperglycaemia and adverse pregnancy outcomes (HAPO) study.Results: The cohort consisted of 58,297 mother-child pairs. Of those, 7245 had a GDM diagnosis and 1407 had a GDM diagnosis with a prescription of insulin. Adverse pregnancy outcomes were higher in both GDM groups compared to the control group. Birthweight (OR 2.08 [95% CI 1.50-2.90]), primary caesarean section (OR 1.70 [95% CI 1.48-1.95]), intensive neonatal care (OR 1.25 [95% CI 1.04-1.50]), preeclampsia (OR 1.51 [95% CI 1.23-1.85]), and clinical neonatal hypoglycaemia (OR 5.32 [95% CI 4.27-6.62]) were higher in the GDM+insulin group in comparison to a control group after adjustment for potential confounders.Conclusion: Most of the adverse pregnancy outcomes were moderately higher in both identified GDM groups in comparison to women without GDM. Women receiving insulin treatment are at an increased risk of most of the defined adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Steven Offenbacher was one of the first researchers to identify periodontal disease as a risk factor for various adverse pregnancy outcomes. Cohort and case-controlled studies of pregnant women have demonstrated periodontal disease as a risk factor for preterm birth, preeclampsia, and fetal growth restriction. Periodontal therapy during the second trimester improves maternal oral health but fails to reduce the risk of preterm birth. A possible association between periodontal disease and gestational diabetes has also been reported. In one model, periodontal bacteria gain access to the systemic circulation, and thereby the placenta, resulting in local inflammation, placental dysfunction, and, consequently, adverse pregnancy outcomes. It is crucial to increase awareness of the links between maternal periodontal and adverse pregnancy outcomes and to promote oral health prophylaxis during pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Severe hypoxia exists in placentas during early pregnancy, with reoxygenation during mid-gestation. Hypoxia-inducible factor-1α (Hif1α), an oxygen sensor, initiates placental vascular development. We have shown that the placental vasculature in Hmox1-deficient (Hmox1+/-, Het) pregnancies is impaired, with morphological defects similar to Hif1α-deficient placentas.Materials and Methods: Whole wild-type (WT) and Het mouse placentas were collected at E8.5 (1%-3% O2) and E9.5-15.5 (8%-10% O2). mRNA levels were determined using real-time RT-PCR or PCR arrays and protein levels using Western blot. Bone marrow-derived macrophages (BMDMs) from WT, Het, and Hmox1 knockout (KO) mice, representing different Hmox1 cellular levels, were generated to study the role of Hmox1 on Hif1α 's response to hypoxia-reoxygenation and gestational age-specific placental lysates.Results: Hif1α was expressed in WT and Het placentas throughout gestation, with protein levels peaking at E8.5 and mRNA levels significantly upregulated from E9.5-E13.5, but significantly lower in Het placentas. Genes associated with angiogenesis (Vegfa, Vegfr1, Mmp2, Cxcl12, Angpt1, Nos3), antioxidants (Sod1, Gpx1), and transcription factors (Ap2, Bach1, Nrf2) were significantly different in Het placentas. In response to in vitro hypoxia-reoxygenation and to WT or Het placental lysates, Hif1α transcription was lower in Het and Hmox1 KO BMDMs compared with WT BMDMs.Discussion: These findings suggest that deficiencies in Hmox1 underlie the insufficient placental Hif1α response to hypoxia-reoxygenation during gestation and subsequently impair downstream placental vascular formation. Therefore, a dysregulation of Hif1α expression caused by any genetic defect or environmental influence in early pregnancy could be the root cause of pregnancy disorders. [ABSTRACT FROM AUTHOR]

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Introduction: Women with adverse pregnancy outcomes (APOs) have excess risk of later life cardiovascular disease (CVD) perhaps related to an underlying high-risk vascular phenotype. We sought to determine if placental evidence of maternal malperfusion in uncomplicated pregnancies is associated with an increased risk of APOs in subsequent pregnancies.Methods: 536 women with more than one delivery and an initial uncomplicated pregnancy with placental pathology examination between 2008 and 2012 were included. APOs (small for gestational age, preterm delivery, or preeclampsia) were identified for each delivery. Multivariable log-binomial regression was used to estimate the risk of an APO in a subsequent pregnancy associated with MVM lesions in index pregnancy with adjustment for covariates.Results: Placental pathology from the initial pregnancy was compared between women with no APO in any pregnancy (-APO/-APO; n = 403) and women with an initial uncomplicated pregnancy and a subsequent adverse outcome (-APO/+APO; n = 133). Women with MVM lesions had an increased risk of an APO in a subsequent pregnancy relative to women with no MVM lesions after adjusting for covariates (aOR = 1.61; 95%CI = 1.06-2.46). Decidual vasculopathy was found in 13/133 (9.8%) of -APO/+APO women compared with 16/403 (4.0%) of -APO/-APO women, with an adjusted odds ratio of 2.51 (95% CI = 1.31-4.80).Discussion: MVM lesions found in placentas in uncomplicated pregnancies are associated with an increased risk of an adverse outcome in a subsequent pregnancy. Placental evidence of vascular malperfusion could offer a novel approach to risk stratification for subsequent pregnancy complications and perhaps future CVD. [ABSTRACT FROM AUTHOR]

Introduction: The biological mechanisms that underlie racial disparities in placenta-mediated pregnancy complications remain unknown. Placental evidence of maternal vascular malperfusion (MVM), a common pathologic feature of these outcomes, represents hypoxic-ischemic damage to the placenta. We sought to separately estimate the risk of MVM and individual lesions associated with maternal race.Methods: This was a retrospective cohort study of black and white women with singleton live births and placental pathology data at Magee-Womens Hospital during 2008-2012 (n = 15,581). MVM consisted of ≥1 individual lesions: low placental weight, decidual vasculopathy, accelerated villous maturation, infarcts, and fibrinoid deposition. We separately compared the incidence of MVM and individual lesions in black and white women using logistic regression with generalized estimating equations.Results: After adjusting for covariates, black women had increased risks of MVM (aOR 1.14, 95% CI 1.05-1.23), low placental weight (aOR 1.41, 95% CI 1.28-1.55), and decidual vasculopathy (aOR 1.58, 95% CI 1.36-1.83), also observed in uncomplicated, preterm, and term births. Conversely, black women had decreased risk of infarcts (aOR 0.84, 95% CI 0.75-0.95) compared with white women, also observed in uncomplicated and full-term births. Race was not associated with accelerated villous maturation or fibrinoid deposition. Inverse probability weighting to account for potential selection bias generated similar results.Discussion: Our findings suggest that excess risks of MVM, specifically low placental weight and decidual vasculopathy in black women may be due to a pathological susceptibility to an underlying high-risk vascular phenotype. The clinical significance of race differences in the occurrence of infarcts warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Chronic histiocytic intervillositis (CHI) of the placenta although rare, has a high recurrence rate, is associated with serious adverse pregnancy outcomes and has no available treatment. This study aims to determine clinical, biochemical and radiological factors associated with CHI, to guide management of subsequent pregnancies.Methods: This retrospective observational study included consecutive cases with a histopathologic diagnosis of CHI after 18 weeks of gestation, between 2001 and 2014, and no controls. Clinical (maternal, fetal and delivery outcomes), biochemical (first- and second-trimester biomarkers for fetal aneuploidy and serum alkaline phosphatase) and radiological (second- and third-trimester fetal, placental and Doppler ultrasound) factors associated with a histopathological diagnosis of CHI were identified and results presented as percentages. Outcomes of subsequent pregnancies were described.Results: Of 231 identified cases of 'intervillositis', 33 were confirmed to have CHI, of which only 4/33 (12.1%) had prior uncomplicated term deliveries. During pregnancy, 10/18 (55.5%) had abnormal first-trimester screening, 4/16 (25%) had abnormal second-trimester screening, 6/19 (31.6%) had at least one elevated alkaline phosphatase level, and 15/20 (75%) had at least one abnormal feature on mid-trimester placental ultrasound. In subsequent pregnancies that were closely followed with a combination of biochemical and radiologic tests, there were no cases of fetal loss, and lower incidence of fetal growth restriction and preterm birth.Discussion: No clinical, biochemical or radiological finding is consistently associated with CHI and adverse outcomes thereof. Whether the incorporation of these tests in individualized care-plans could improve outcomes in subsequent pregnancies needs to be studied further. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States.Objective: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin.Study Design: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models.Results: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis.Conclusion: Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation. [ABSTRACT FROM AUTHOR]

Background: Histologic examination of the placenta is often performed after preterm birth. Although placental examination cannot change the index pregnancy outcome, it may inform the risk of adverse outcomes in a subsequent pregnancy. Previous research has examined the association between individual histologic lesions and pregnancy outcomes without consistent results.Objective: This study aimed to determine the independent contributions of the major placental pathology histologic types to recurrent preterm birth.Study Design: This was a retrospective cohort study of deliveries at a tertiary care center from January 2009 to March 2018. Individuals with ≥2 births, an index birth of <37 weeks of gestation, and a placental pathology report from the index pregnancy were included. The presence of maternal vascular malperfusion, fetal vascular malperfusion, acute inflammation, and chronic inflammation was extracted from the pathology reports for each index placenta and classified as none, low grade, or high grade. A log-binomial model incorporating all 4 placental pathology histologic types, index gestational age, race, and maternal age was used to estimate the associations between each placental histologic type and risk of recurrent preterm birth. Moreover, 2-way interaction terms were studied among placental histologic types. In addition, 2 stratified analyses were completed on the basis of characteristics of the index preterm birth: (1) by late preterm (gestational age of 34-36 weeks) vs early-to-moderate preterm birth (<34 weeks) and (2) a subgroup analysis of those with spontaneous preterm birth.Results: A total of 924 pregnancy pairs met the inclusion criteria. Only high-grade chronic inflammation was independently associated with an increased risk of recurrent preterm birth (adjusted risk ratio, 1.37; 95% confidence interval, 1.03-1.81). Stratified analysis by gestational age group demonstrated maternal vascular malperfusion was associated with recurrent preterm birth only among those with early preterm birth (adjusted risk ratio, 1.40; 95% confidence interval, 1.01-1.93). Among participants with spontaneous preterm labor, no association was found between pathology histologic types and risk of preterm birth.Conclusion: Among index preterm pregnancies, high-grade chronic placental inflammation was associated with recurrent preterm birth. Low-grade maternal vascular malperfusion was associated with recurrent preterm birth only among those with an early or moderate index preterm birth (<34 weeks of gestation). These findings may be useful in determining the risk profile for individual patients and may generate hypotheses as to the pathogenesis of recurrent preterm birth. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Lack of trace elements during pregnancy is detrimental to maternal and fetal health. Our aim is to study the changes in trace element levels in Chinese pregnant women and their association with adverse pregnancy outcomes. PATIENTS AND METHODS: 1568 cases of Chinese pregnant women in remote areas were collected for a prospective cohort study. Serum copper, zinc, calcium and iron levels were measured at pre-pregnancy, 1st trimester (7w-12w), 2nd trimester (24w-28w) and 3rd trimester (35w-40w). RESULTS: (1) Serum copper levels was significantly higher after pregnancy than before, calcium and iron levels decreased, but zinc levels did not change significantly. (2) Copper and zinc deficiency in pregnant women was not a common finding, but lack of iron and calcium was frequently encountered; iron deficiency was especially common in the 3rd trimester (42.27%). (3) Serum zinc and iron levels in patients who either had a miscarriage or a preterm delivery were significantly lower than in the control group (p < 0.05). In patients with premature rupture of membranes, serum zinc levels were significantly lower (p < 0.05). In patients with intrauterine growth restriction (IUGR), serum copper, zinc, calcium and iron were significantly lower (p < 0.05). CONCLUSIONS: Trace elements is closely associated with fetal growth and development during pregnancy. Deficiency can lead to adverse pregnancy outcomes. Therefore, we should have a reasonable diet, replenish trace elements, therefore reducing the occurrence of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

To investigate the levels of Prokineticin-1 (PROK1) and matrix metalloproteinase-2 (MMP-2) in second-trimester amniotic fluid (AF). AF samples were investigated in 81 patients. AF-PROK1 and AF-MMP-2 were not significantly associated with adverse pregnancy outcomes (preeclampsia, intrauterine growth retardation, spontaneous preterm birth, gestational diabetes, gestational hypertension). AF-PROK1 levels in patients with abnormal first-trimester screening were significantly higher than those who underwent amniocentesis due to abnormal second-trimester screening tests (p = .04). AF-PROK1 or AF-MMP-2 do not have a role in the prediction of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Recently, metabolic dysfunction–associated fatty liver disease (MAFLD), rather than nonalcoholic fatty liver disease (NAFLD), was proposed to better describe liver disease associated with metabolic dysfunction (MD). In this study, we attempted to investigate the impact of MAFLD on pregnancy complications. The current study is a secondary analysis of a multicenter prospective cohort designed to examine the risk of NAFLD during pregnancy. In the first trimester, enrolled pregnant women were evaluated for hepatic steatosis by liver ultrasonography, and blood samples were collected for biochemical measurements. The study population was divided into 3 groups: no NAFLD, hepatic steatosis but without metabolic dysfunction (non-MD NAFLD), and MAFLD. The primary outcome was the subsequent development of adverse pregnancy outcomes, including gestational diabetes mellitus, pregnancy-associated hypertension, preterm birth, and fetal growth abnormalities. The study population consisted of 1744 pregnant women, including 1523 with no NAFLD, 43 with non-MD NAFLD, and 178 with MAFLD. The risk of subsequent development of adverse pregnancy outcomes was higher in MAFLD than in non-MD NAFLD (adjusted odds ratio, 4.03; 95% CI, 1.68–9.67), whereas the risk was not significantly different between no NAFLD and non-MD NAFLD. Among women with no NAFLD, the presence of MD increased the risk of adverse pregnancy outcomes. However, women with MAFLD were at higher risk for adverse pregnancy outcomes than women with no NAFLD without MD or those with no NAFLD with MD. In pregnant women, MAFLD may be associated with an increased risk of subsequent adverse pregnancy outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) is one of the most important polybrominated diphenyl ethers (PBDEs) congeners, and epidemiological studies have shown that it can cause adverse pregnancy outcomes. The aim of our study was to investigate the role of placental injury in BDE-47-induced adverse pregnancy outcomes through in vivo and in vitro models. From day 0.5 to day 16.5 of pregnancy of ICR mice, BDE-47 oral doses of 0, 25, 50 and 100 mg/kg/day were administered. Immunohistochemical staining found that BDE-47 inhibited the expression of CD34 in mouse placenta, and ELISA results showed that BDE-47 reduced the levels of VEGF and PlGF in the serum of pregnant mice. Western blot assays found that the expression levels of VEGF-A and invasion-related factors were decreased in the placentas of BDE-47-treated group, which indicated that BDE-47 could impair placental angiogenesis. Furthermore, BDE-47 inhibited proliferation, increased apoptosis and autophagy, and activated p38 MAPK signaling pathway in mouse placental tissue. In vitro, HTR-8/SVneo cells were treated with 0, 5, 10, 20 μM BDE-47 for 24 h. Wound healing assays and Transwell assays showed that BDE-47 inhibited the migration and invasion ability of HTR-8/SVneo cells. We also found that BDE-47 inhibited the proliferation of HTR-8/SVneo cells and increased apoptosis and autophagy. BDE-47 activated p38 MAPK signaling pathway in HTR-8/SVneo cells, and inhibition of p38 MAPK signaling pathway in HTR-8/SVneo cells restored the effects caused by BDE-47. In conclusion, BDE-47 impairs placental angiogenesis by inhibiting cell migration and invasion, and induces placental toxicity by inhibiting proliferation, increasing apoptosis and autophagy. In vitro , activation of p38 MAPK signaling pathway is involved in the processes of placental injury by BDE-47. [Display omitted] • BDE-47 causes adverse pregnancy outcomes by impairing the structure and function of the placenta. • BDE-47 attenuates cell migration and invasion ability in mouse placenta and HTR-8/SVneo cells. • BDE-47 inhibits proliferation and promotes apoptosis and autophagy in mouse placenta and HTR-8/SVneo cells. • BDE-47 activates the p38 MAPK signaling pathway in mouse placenta and HTR-8/SVneo cells. • The p38 MAPK signaling pathway is involved in the effect of BDE-47 on HTR-8/SVneo cells. [ABSTRACT FROM AUTHOR]

Maternal obesity in pregnancy is associated with increased maternal and fetal risks. Pregnancy management should include counseling, screening, and optimization of maternal health, increased fetal surveillance, and preparation for parturition. A multidisciplinary approach should be implemented including collaboration from obstetricians, nutritionists, anesthesiologists, social workers, and neonatologists to optimize perinatal outcomes. Pregnancy is an ideal window of opportunity to influence both the patient’s long-term health and the health of the offspring. [ABSTRACT FROM AUTHOR]

Background: Endometriosis and uterine fibroids are common gynecologic conditions associated with a greater risk for infertility. Previous research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially because of increased utilization of fertility treatments.Objective: Our objective was to investigate whether women with a history of endometriosis or fibroids had a greater risk for adverse pregnancy outcomes and whether this risk varied by infertility history and fertility treatment utilization.Study Design: Deliveries (2013-2017) recorded in Massachusetts' vital records were linked to assisted reproductive technology data, hospital stays, and all-payer claims database. We identified endometriosis and fibroids diagnoses via the all-payer claims database before index delivery. Adjusted relative risks for pregnancy complications were modeled using generalized estimating equations with a log link and Poisson distribution. The influence of subfertility or infertility and assisted reproductive technology was also investigated.Results: Among 91,825 deliveries, 1560 women had endometriosis and 4212 had fibroids. Approximately 30% of women with endometriosis and 26% of women with fibroids experienced subfertility or infertility without utilizing assisted reproductive technology, and 34% of women with endometriosis and 21% of women with fibroids utilized assisted reproductive technology for the index delivery. Women with a history of endometriosis or fibroids were at a greater risk for pregnancy-induced hypertension, preeclampsia, or eclampsia (endometriosis relative risk, 1.17; fibroids relative risk, 1.08), placental abnormalities (endometriosis relative risk, 1.65; fibroids relative risk, 1.38), and cesarean delivery (endometriosis relative risk, 1.22; fibroids relative risk, 1.17) than women with no history of those conditions. Neonates born to women with a history of endometriosis or fibroids were also at a greater risk for preterm birth (endometriosis relative risk, 1.24; fibroids relative risk, 1.17). Associations between fibroids and low birthweight varied by fertility status or assisted reproductive technology (P homogeneity=.01) and were stronger among noninfertile women.Conclusion: Endometriosis or fibroids increased the risk for adverse pregnancy outcomes, possibly warranting differential screening or treatment. [ABSTRACT FROM AUTHOR]

Introduction Heparin is often prescribed during pregnancy with the intention of improving perinatal outcomes on the basis that it exerts an anticoagulant action in the inter-villous space. Accumulating in-vitro and in-vivo evidence indicates that heparin's beneficial effects in pregnancy may result from ‘non-anticoagulant’ effects including the promotion of angiogenesis. Methods To study the effect of heparin within the placenta, we performed secondary analyses on a pilot trial where 32 women with negative thrombophilia screens and second-trimester evidence of placental insufficiency were randomized to standard care or antenatal self-administration of unfractionated heparin (UFH) 7500IU twice-daily. Serial placental ultrasound images were reviewed and compared with histo-pathologic findings following delivery. Results There were no differences between the two arms in either the evolution of abnormal placental lesions on ultrasound ( p = 0.75) or evidence of maternal vascular under-perfusion on histopathology ( p = 0.89). In pregnancies considered at increased risk for adverse pregnancy outcomes based on previous history or abnormal serum marker screen, early (second-trimester) placental ultrasound, reflecting developmental pathology had better test characteristics (sensitivity 77.8%; positive predictive value 80.8%) for predicting adverse pregnancy outcomes than third-trimester ultrasound that is reflective of placental thrombotic injury. Conclusions Administration of UFH did not prevent the development or evolution of abnormal placental lesions on placental ultrasound or evidence of maternal vascular underperfusion on placental histo-pathology. Second-trimester placental ultrasound may be of value in predicting those at greatest risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate alterations in gut microbiota after exposure to air pollutants during pregnancy and its mediation effect in inducing adverse pregnancy outcomes (APOs). Participants (n = 916) were enrolled between 2017 and 2018 from a prospective cohort study of pregnant women in Guangzhou, China. The relative abundance of fecal microbiota was profiled using 16SrRNA V4 region sequencing. Exposure to air pollutants in each trimester of pregnancy was assessed using measurements from the nearest monitoring station. APOs including pre-term birth (PTB), post-term birth (POTB), low birth weight (LBW), macrosomia fetus (MF), birth defects (BDs), pathological cesarean section (PCS) and postpartum hemorrhage (PPH)) were determined by referring to reliable clinical records and diagnostic criteria. Univariate analysis, multivariate analysis and mediation analysis were performed to estimate the association among air pollutants, gut microbiota and APOs. Air pollutants exposure during pregnancy was significantly correlated with the alterations in the gut microbiota, and increased risks of various APOs by 1.07–1.36-fold (P < 0.05). The mediation analyses indicated that alterations in Eggerthella , Phascolarctobacterium and Clostridium partially mediated the effects of air pollutants exposure (PM 2.5 , PM 10 , O 3 , NO 2 and SO 2) on APOs. The relative abundance of f_ Micrococcaceae explained 11.39%, 64.90% and 54.80% of the correlation between SO 2 , PM 2.5 , PM 10 and POTB, respectively; whereas g_ Rothia ex plained 11.97%, 67.80% and 54.50%, respectively. g_ Parabacteroides ex plained 53.0% of the correlation between PM 2.5 and PTB. Increased air pollutants exposure during pregnancy may induce adverse pregnancy outcomes via alteration of the gut microbiota. • Air pollutants exposures during pregnancy was associated with alterations in the gut microbiota and increased risks of APOs. • Various APOs were associated with gut microbiotas that were associated with air pollutants exposures. • Alterations in the gut microbiota may partially mediate the effects of air pollutants exposures on APOs. • Potential roles of gut microbes to prevent or treat APOs induced by air pollutions exposure. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy outcomes (APOs). Material & Methods: Human, experimental and in vitro studies were evaluated. Results: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circulation and amniotic fluid. Their presence in the foeto‐placental compartment can stimulate a foetal immune/inflammatory response characterized by the production of IgM antibodies against the pathogens and the secretion of elevated levels of inflammatory mediators, which in turn may cause miscarriage or premature birth. Moreover, infection/inflammation may cause placental structural changes leading to pre‐eclampsia and impaired nutrient transport causing low birthweight. Foetal exposure may also result in tissue damage, increasing the risk for perinatal mortality/morbidity. Finally, the elicited systemic inflammatory response may exacerbate local inflammatory responses at the foeto‐placental unit and further increase the risk for APOs. Conclusions: Further investigation is still necessary to fully translate the findings of basic research into clinical studies and practice. Understanding the systemic virulence potential of the individual's oral microbiome and immune response may be a distinctly different issue from categorizing the nature of the challenge using clinical signs of PD. Therefore, a more personalized targeted therapy could be a more predictive answer to the current “one‐size‐fits‐all” interventions. [ABSTRACT FROM AUTHOR]

Background: Pregnancy sometimes has adverse outcomes including low birthweight (<2500 g), pre‐term birth (<37 weeks), growth restriction, pre‐eclampsia, miscarriage and/or stillbirth. Maternal periodontitis directly and/or indirectly have potential to influence the health of the foetal–maternal unit. Aims: To assess the epidemiological evidence for the impact of periodontal disease on adverse pregnancy outcomes and to identify potential underpinning mechanisms. Epidemiology: Low birthweight, pre‐term birth and pre‐eclampsia have been associated with maternal periodontitis exposure. However, the strength of the observed associations is modest and seems to vary according to the population studied, the means of periodontal assessment and the periodontal disease classification employed. Biological mechanisms: Two major pathways have been identified, One direct, in which oral microorganisms and/or their components reach the foetal–placental unit and one indirect, in which Inflammatory mediators circulate and impact the foetal–placental unit. Interventions: Although periodontal therapy has been shown to be safe and leads to improved periodontal conditions in pregnant women, case‐related periodontal therapy, with or without systemic antibiotics does not reduce overall rates of pre‐term birth and low birthweight. Guidelines: Given the current evidence, various treatment strategies could be evaluated that consider specific target populations, as well as timing and intensity of treatment. [ABSTRACT FROM AUTHOR]

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Copyright of Canadian Journal of Dental Hygiene is the property of Canadian Dental Hygienists Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Previous research regarding pregnancy outcomes in women with psoriasis either used selective hospital-based data, or analyzed obstetric, but not infant-specific, outcomes. Objective: We sought to investigate whether maternal psoriasis was associated with increased risk of adverse pregnancy outcomes, compared with unaffected mothers, in an unselected nationwide population-based data set. Methods: In total, 1463 mothers with psoriasis and 11,704 randomly selected mothers without psoriasis were included. Of the 1463 mothers with psoriasis, 645 (44.1%) who had received photochemotherapy or systemic therapy within 2 years before their index deliveries were put in the severe psoriasis group. Conditional logistic regression analyses were conducted to calculate the risk of low birth weight (LBW), preterm birth, cesarean section, small for gestational age, and preeclampsia or eclampsia for these two groups, after adjusting for characteristics of the mother, father, and infant. Results: The odds of LBW for women with severe psoriasis were 1.40 times those of mothers without psoriasis (95% confidence interval = 1.04-1.89) after adjusting for characteristics of the mother, father, and infant. However, mothers with mild psoriasis had no significantly higher odds of LBW, preterm birth, cesarean section, infants small for gestational age, and preeclampsia or eclampsia compared with those without psoriasis. Limitations: Patients with psoriasis were identified by diagnostic code in database, resulting in the possibility of misclassification bias. In addition, lack of information regarding maternal risk behaviors and previous adverse pregnancy outcomes may leave residual confounding. Conclusion: We found that pregnant women with severe psoriasis had an increased risk of LBW infants, whereas mild psoriasis was not associated with excess risk of adverse birth outcomes. [Copyright &y& Elsevier]

Background: Women with gestational glucose intolerance, defined as an abnormal initial gestational diabetes mellitus screening test, are at risk of adverse pregnancy outcomes even if they do not have gestational diabetes mellitus. Previously, we defined the physiological subtypes of gestational diabetes mellitus based on the primary underlying physiology leading to hyperglycemia and found that women with different subtypes had differential risks of adverse outcomes. Physiological subclassification has not yet been applied to women with gestational glucose intolerance.Objective: We defined the physiological subtypes of gestational glucose intolerance based on the presence of insulin resistance, insulin deficiency, or mixed pathophysiology and aimed to determine whether these subtypes are at differential risks of adverse outcomes. We hypothesized that women with the insulin-resistant subtype of gestational glucose intolerance would have the greatest risk of adverse pregnancy outcomes.Study Design: In a hospital-based cohort study, we studied women with gestational glucose intolerance (glucose loading test 1-hour glucose, ≥140 mg/dL; n=236) and normal glucose tolerance (glucose loading test 1-hour glucose, <140 mg/dL; n=1472). We applied homeostasis model assessment to fasting glucose and insulin levels at 16 to 20 weeks' gestation to assess insulin resistance and deficiency and used these measures to classify women with gestational glucose intolerance into subtypes. We compared odds of adverse outcomes (large for gestational age birthweight, neonatal intensive care unit admission, pregnancy-related hypertension, and cesarean delivery) in each subtype to odds in women with normal glucose tolerance using logistic regression with adjustment for age, race and ethnicity, marital status, and body mass index.Results: Of women with gestational glucose intolerance (12% with gestational diabetes mellitus), 115 (49%) had the insulin-resistant subtype, 70 (27%) had the insulin-deficient subtype, 40 (17%) had the mixed pathophysiology subtype, and 11 (5%) were uncategorized. We found increased odds of large for gestational age birthweight (primary outcome) in women with the insulin-resistant subtype compared with women with normal glucose tolerance (odds ratio, 2.35; 95% confidence interval, 1.43-3.88; P=.001; adjusted odds ratio, 1.74; 95% confidence interval, 1.02-3.48; P=.04). The odds of large for gestational age birthweight in women with the insulin-deficient subtype were increased only after adjustment for covariates (odds ratio, 1.69; 95% confidence interval, 0.84-3.38; P=.14; adjusted odds ratio, 2.05; 95% confidence interval, 1.01-4.19; P=.048). Among secondary outcomes, there was a trend toward increased odds of neonatal intensive care unit admission in the insulin-resistant subtype in an unadjusted model (odds ratio, 2.09; 95% confidence interval, 0.99-4.40; P=.05); this finding was driven by an increased risk of neonatal intensive care unit admission in women with the insulin-resistant subtype and a body mass index of <25 kg/m2. Infants of women with other subtypes did not have increased odds of neonatal intensive care unit admission. The odds of pregnancy-related hypertension in women with the insulin-resistant subtype were increased (odds ratio, 2.09; 95% confidence interval, 1.31-3.33; P=.002; adjusted odds ratio, 1.77; 95% confidence interval, 1.07-2.92; P=.03) compared with women with normal glucose tolerance; other subtypes did not have increased odds of pregnancy-related hypertension. There was no difference in cesarean delivery rates in nulliparous women across subtypes.Conclusion: Insulin-resistant gestational glucose intolerance is a high-risk subtype for adverse pregnancy outcomes. Delineating physiological subtypes may provide opportunities for a more personalized approach to gestational glucose intolerance. [ABSTRACT FROM AUTHOR]

Background: Antenatal depression affects approximately 1 of 7 pregnancies, with an increasing prevalence across gestation. Data regarding the associations between antenatal depression and adverse pregnancy outcomes yielded conflicting results. However, previous studies evaluated the cross-sectional prevalence of depression at various time points and not the depressive symptom trajectory across gestation.Objective: This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes.Study Design: This was a secondary analysis of a large multisite prospective cohort of nulliparous women across the United States. The Edinburgh Postpartum Depression Scale was administered at 2 study visits: between 6 and 14 weeks' gestation and between 22 and 30 weeks' gestation. The Edinburgh Postpartum Depression Scale score trajectories were categorized as improved, stable, or worsened based on whether the scores changed by at least 1 standard deviation between the 2 visits. The frequencies of adverse pregnancy outcomes (hypertensive disorders of pregnancy, abruption, cesarean delivery, preterm birth [ie, <37 weeks' gestation], small for gestational age neonates, neonatal intensive care unit admission, and maternal readmission) were compared with depression trajectories across gestation in bivariable and multivariable analyses. Secondary analyses evaluated the frequencies of spontaneous and medically indicated preterm births and frequencies of spontaneous and medically indicated preterm births before 35, 32, and 28 weeks' gestation.Results: Of the 8784 women who completed the 2 antenatal Edinburgh Postpartum Depression Scale screens, 1141 (13.0%) had improved, 6663 (75.9%) had stable, and 980 (11.2%) had worsened depressive symptom trajectories across gestation. Compared with women with improved or stable depressive symptoms, those with worsened symptoms were more likely to experience preterm birth (8.3% vs 7.4% vs 9.9%, respectively; P=.018). After controlling for potential confounders, worsened depressive symptoms remained associated with more frequent preterm birth (adjusted odds ratio, 1.68; 95% confidence interval, 1.10-2.57).Conclusion: Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth. [ABSTRACT FROM AUTHOR]

Adverse pregnancy outcome (APO), includes fetal loss ≥20 weeks’ gestation (fetal death), severe preeclampsia <36 weeks, or severe intrauterine growth restriction (severe IUGR) defined as birth weight ≤5th percentile or ≤10th percentile for gestational age. APO affects 8% of pregnant women (320,000 annually) and collectively contributes to the largest proportion of maternal/fetal mortality and morbidity. Women with prior APO in antecedent pregnancy are at high risk of an adverse maternal or fetal outcome in the subsequent pregnancy. Maternal serum markers and Doppler ultrasound can be used to predict adverse pregnancy outcome. There are no adequate, completed randomized trials for prophylactic measures; the roles of aspirin, calcium, and low molecular weight heparin need to be evaluated. [Copyright &y& Elsevier]

Objective: The purpose of this study was to investigate associations between fetal inherited thrombophilia and adverse pregnancy outcomes, including pregnancy-induced hypertensive disorders (PIHD), antepartum hemorrhage (APH), small-for-gestational age <10th percentile (SGA), and preterm birth (PTB). Study design: Seven hundred and seventeen cases and 609 controls were genotyped for Factor V Leiden (FVL, G1691A), Prothrombin gene mutation (PGM, G20210A), and Methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C using DNA from newborn screening cards. Results: For babies born <28 weeks' gestation, PGM was associated with an increased risk of SGA (OR 6.40, 95%CI 1.66–24.71) and APH with SGA (OR 6.35, 95%CI 1.63–24.75). Homozygous MTHFR A1298C was associated with an increased risk of SGA for babies born 28–31 weeks gestation (OR 4.00, 95%CI 1.04–15.37), and with APH and SGA for babies born <32 weeks' gestation (OR 3.57, 95%CI 1.09–11.66). Homozygous MTHFR C677T was associated with a reduced risk of PTB and SGA (OR 0.52, 95%CI 0.28–0.96) for babies born 32 to 36 weeks' gestation. Homozygous FVL decreased the risk of PTB <32 weeks' gestation (OR 0.55, 95%CI 0.31<0.98). Conclusion: Fetal thrombophilic polymorphisms may be related to adverse pregnancy outcomes, in particular SGA. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to investigate the association between congenital heart defects (CHD), and maternal homocysteine, smoking, and the MTHFR 677 C>T polymorphism. Study design: Plasma homocysteine concentrations, smoking status, and MTFHR 677 genotypes were determined in 275 white women who had pregnancies affected by CHDs and 118 white women who had a normal pregnancy. Results: Homocysteine concentrations were significantly higher among women who had affected pregnancies (P < .0001). The highest estimated risk for having a CHD-affected pregnancy was among women who were smokers, were in the highest quartile for homocysteine, and had the MTHFR 677 CC genotype (odds ratio [OR] 11.8; 95% CI 2.6–53.3). Conclusion: Many CHDs are due to a complex interaction between lifestyle factors and genetic susceptibilities. Our results suggest that the combined effect of elevations in maternal homocysteine, smoking, and the MTHFR 677 C>T polymorphism increase the risk of having a CHD-affected pregnancy. [ABSTRACT FROM AUTHOR]

Background: The diagnostic criteria for preeclampsia have evolved from the traditional definition of de novo hypertension and proteinuria to a broader definition of hypertension with evidence of end-organ dysfunction. Although this change is endorsed by various societies such as the International Society for the Study of Hypertension in Pregnancy and the American College of Obstetricians and Gynecologists, there remains controversy with regard to the implementation of broader definitions and the most appropriate definition of end-organ dysfunction.Objective: This study aimed to assess the impact of different diagnostic criteria for preeclampsia on rates of disease diagnosis, disease severity, and adverse outcomes and to identify associations between each component of the different diagnostic criteria and adverse pregnancy outcomes.Study Design: We performed a retrospective cohort study of singleton pregnancies at Monash Health between January 1, 2016 and July 31, 2018. Within this population, all cases of gestational hypertension and preeclampsia were reclassified according to the International Society for the Study of Hypertension in Pregnancy 2001, American College of Obstetricians and Gynecologists 2018, and International Society for the Study of Hypertension in Pregnancy 2018 criteria. Differences in incidence of preeclampsia and maternal and perinatal outcomes were compared between the International Society for the Study of Hypertension in Pregnancy 2001 group and the extra cases identified by American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018. Outcomes assessed included biochemical markers of preeclampsia, a composite of adverse maternal outcomes, and a composite of adverse perinatal outcomes. Multiple logistic regression analysis was also performed to assess each component of the American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018 criteria and their associations with adverse maternal and perinatal outcomes.Results: Of 22,094 pregnancies, 751 (3.4%) women had preeclampsia as defined by any of the 3 criteria. Compared with International Society for the Study of Hypertension in Pregnancy 2001, the American College of Obstetricians and Gynecologists 2018 criteria identified an extra 42 women (n=654 vs n=696, 6.4% relative increase) with preeclampsia, and International Society for the Study of Hypertension in Pregnancy 2018 identified an extra 97 women (n=654 vs n=751, 14.8% relative increase). The additional women identified by International Society for the Study of Hypertension in Pregnancy 2018 exhibited a milder form of disease with lower rates of severe hypertension (62.4% vs 44.3%; P<.01) and magnesium sulfate use (11.9% vs 4.1%; P<.05) and a trend toward lower rates of adverse maternal outcomes (9.8% vs 4.1%). These women also delivered at a later gestation, and their babies had a lower number of neonatal intensive care unit admissions and adverse perinatal outcomes. Objective features such as fetal growth restriction, thrombocytopenia, renal and liver impairment, and proteinuria were associated with an increased risk of adverse maternal and perinatal outcomes, whereas subjective neurologic features demonstrated poorer associations.Conclusion: Implementation of broader definitions of preeclampsia will result in an increased incidence of disease diagnosis. However, because women who exclusively fulfill the new criteria have a milder phenotype of the disease, it remains uncertain whether this will translate to improved outcomes. [ABSTRACT FROM AUTHOR]

• Interferon-beta exposure in pregnancy did not increase adverse pregnancy outcomes. • The result remained after stratification by maternal characteristics. • The result also remained, when stratifying by newborn characteristics. • Interferon-beta exposure in pregnancy does not appear to be harmful for the newborn. Previous studies reported no increase in the prevalence of adverse pregnancy outcomes after exposure to interferon-beta (IFN-beta). However, no study has investigated if the prevalence of these outcomes after IFN-beta exposure is modified by maternal and newborn characteristics. Our objective was to describe the stratified prevalence of adverse pregnancy outcomes among women with multiple sclerosis (MS) exposed only to IFN-beta or unexposed to any MS disease modifying drugs (MSDMDs). This population-based cohort study using Finnish (1996-2014) and Swedish (2005-2014) register data included pregnancies of women with MS exposed only to IFN-beta 6 months before or during pregnancy (n=718) or unexposed to MSDMDs (n=1397). The outcome prevalences were described stratified by maternal and newborn characteristics, with 95% confidence intervals (CIs). Confounder-adjusted analyses were performed if the prevalence results indicated modified effect of IFN-beta in specific strata. The stratified analysis indicated that the prevalence of serious (anomaly or stillbirth) and other adverse pregnancy outcomes was similar among the exposed and unexposed, with no statistically significant difference. Among women treated for MS >5 years, serious adverse pregnancy outcomes occurred in 4.3% (95%CI: 1.9-8.3%) of pregnancies exposed only to IFN-beta 6 months before or during pregnancy and in 2.7% (95%CI: 1.2-5.0%) of unexposed pregnancies. The confounder adjusted analyses did not support the hypothesis that MS treatment duration before pregnancy would modify the risk of adverse pregnancy outcomes after exposure to IFN-beta 6 months before or during pregnancy. The prevalence of adverse pregnancy outcomes was not increased after IFN-beta exposure, when pregnancies of women with MS were stratified by maternal and newborn characteristics. The stratified results were similar to the unstratified results in the same population. [ABSTRACT FROM AUTHOR]

Background: In routine antenatal care, blood pressure is used as a screening tool for preeclampsia and its associated adverse outcomes. As such women with a blood pressure greater than 140/90 mm Hg undergo further investigation and closer follow-up, whereas those with lower blood pressures receive no additional care. In the nonpregnant setting, the American College of Cardiology now endorses lower hypertensive thresholds and it remains unclear whether these lower thresholds should also be considered in pregnancy.Objective: (1) To examine the association between lower blood pressure thresholds (as per the American College of Cardiology guidelines) and pregnancy outcomes and (2) to determine whether there is a continuous relationship between blood pressure and pregnancy outcomes and identify the point of a change at which blood pressure is associated with an increased risk of such outcomes.Study Design: This was a retrospective study of singleton pregnancies at Monash Health, Australia. Data were obtained with regards to maternal characteristics and blood pressure measurements at varying gestational ages. Blood pressures were then categorized as (1) mean arterial pressure and (2) normal, elevated, stage 1 and stage 2 hypertension, as per the American College of Cardiology guidelines. Multivariable regression analysis was performed to identify associations between blood pressure categories and pregnancy outcomes.Results: This study included 18,243 singleton pregnancies. We demonstrated a positive dose-response relationship between mean arterial pressure and the development of preeclampsia in later pregnancy. Across all gestational ages, the risk of preeclampsia was greater in those with "elevated blood pressure" and "stage 1 hypertension" in comparison with the normotensive group (adjusted risk ratio; 2.45, 95% confidence interval, 1.74-3.44 and adjusted risk ratio, 6.60; 95% confidence interval, 4.98-8.73 respectively, at 34-36 weeks' gestation). There was also an association between stage 1 hypertension, preterm birth, and adverse perinatal outcomes.Conclusion: This study demonstrated that preeclampsia and the associated adverse outcomes are not exclusive to those with blood pressures greater than 140/90 mm Hg. As such, those with prehypertensive blood pressures may also benefit from closer monitoring. Further research is essential to determine whether lowering the blood pressure threshold in pregnancy would improve detection and outcomes. [ABSTRACT FROM AUTHOR]

Oral health care concerns often are addressed in health care setting where nurses can allay concerns, answer questions, and provide key wellness messages. This article is the 3rd in a series organized around stages of life and is the 1st that focuses on adulthood. Current advice emphasizes the importance of oral health during pregnancy as it can affect both the mother's overall health and the health of the baby. A mother with cavities is more likely to share the bacteria that cause cavities to her child in the 1st few months of life, even before the 1st tooth. This article will describe the crucial messages that a nurse can share that will make a big difference to both mother and child. [ABSTRACT FROM AUTHOR]

Observational studies demonstrate that women with severe periodontitis have a higher risk of adverse pregnancy outcomes like preterm birth and low birthweight. Standard treatment for periodontitis in the form of scaling and root planing during the second trimester failed to reduce the risk of preterm or low birthweight. It is premature to dismiss the association between periodontitis and adverse pregnancy outcomes because one explanation for the failure of scaling and root planing to reduce the risk of adverse pregnancy outcomes is that periodontal pathogens spread to the placental tissue prior to periodontal treatment. In the placenta, orally derived organisms could cause direct tissue damage or mediate a maternal immune response that impairs the growth of the developing fetus. Sequencing studies demonstrate the presence of organisms derived from the oral microbiome in the placenta, but DNA-based sequencing studies should not be the only technique to evaluate the placental microbiome because they may not detect important shifts in the metabolic capability of the microbiome. In humans, polymerase chain reaction and histology have detected periodontal pathogens in placental tissue in association with multiple adverse pregnancy outcomes. We conclude that both placental and oral microbiomes may play a role in periodontitis-associated adverse pregnancy outcomes. However, the measure to determine the association between periodontal pathogens in the placenta and adverse pregnancy outcomes should be the amount and prevalence, not the mere presence of such microorganisms. Placental colonization with periodontal pathogens thus potentially represents the missing link between periodontitis and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether the risk of adverse outcomes in twin pregnancies among subfertile women, conceived with and without in vitro fertilization, differs from those conceived spontaneously.Objective: We sought to evaluate the effects of fertility status on adverse perinatal outcomes in twin pregnancies on a population basis.Study Design: All twin live births of ≥22 weeks' gestation and ≥350 g birthweight to Massachusetts resident women in 2004 through 2010 were linked to hospital discharge records, vital records, and in vitro fertilization cycles. Women were categorized by their fertility status as in vitro fertilization, subfertile, or fertile, and by twin pair genders (all, like, unlike). Women whose births linked to in vitro fertilization cycles were classified as in vitro fertilization; those with indicators of subfertility but without in vitro fertilization treatment were classified as subfertile; all others were classified as fertile. Risks of 6 adverse pregnancy outcomes (gestational diabetes, pregnancy hypertension, uterine bleeding, placental complications [placenta abruptio, placenta previa, and vasa previa], prenatal hospitalizations, and primary cesarean) and 9 adverse infant outcomes (very low birthweight, low birthweight, small-for-gestation birthweight, large-for-gestation birthweight, very preterm [<32 weeks], preterm, birth defects, neonatal death, and infant death) were modeled by fertility status with the fertile group as reference, using multivariate log binomial regression and reported as adjusted relative risk ratios and 95% confidence intervals.Results: The study population included 10,352 women with twin pregnancies (6090 fertile, 724 subfertile, and 3538 in vitro fertilization). Among all twins, the risks for all 6 adverse pregnancy outcomes were significantly increased for the subfertile and in vitro fertilization groups, with highest risks for uterine bleeding (adjusted relative risk ratios, 1.92 and 2.58, respectively) and placental complications (adjusted relative risk ratios, 2.07 and 1.83, respectively). Among all twins, the risks for those born to subfertile women were significantly increased for very preterm birth and neonatal and infant death (adjusted relative risk ratios, 1.36, 1.89, and 1.87, respectively). Risks were significantly increased among in vitro fertilization twins for very preterm birth, preterm birth, and birth defects (adjusted relative risk ratios, 1.28, 1.07, and 1.26, respectively).Conclusion: Risks of all maternal and most infant adverse outcomes were increased for subfertile and in vitro fertilization twins. Among all twins, the highest risks were for uterine bleeding and placental complications for the subfertile and in vitro fertilization groups, and neonatal and infant death in the subfertile group. These findings provide further evidence supporting single embryo transfer and more cautious use of ovulation induction. [ABSTRACT FROM AUTHOR]

Background: Births to subfertile women, with and without infertility treatment, have been reported to have lower birthweights and shorter gestations, even when limited to singletons. It is unknown whether these decrements are due to parental characteristics or aspects of infertility treatment.Objective: The objective of the study was to evaluate the effect of maternal fertility status on the risk of pregnancy, birth, and infant complications.Study Design: All singleton live births of ≥22 weeks' gestation and ≥350 g birthweight to Massachusetts resident women in 2004-2010 were linked to hospital discharge and vital records. Women were categorized by their fertility status as in vitro fertilization, subfertile, or fertile. Women whose births linked to in vitro fertilization cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System were classified as in vitro fertilization. Women with indicators of subfertility but not treated with in vitro fertilization were classified as subfertile. Women without indicators of subfertility or in vitro fertilization treatment were classified as fertile. Risks of 15 adverse outcomes (gestational diabetes, pregnancy hypertension, antenatal bleeding, placental complications [placenta abruptio and placenta previa], prenatal hospitalizations, primary cesarean delivery, very low birthweight [<1500 g], low birthweight [<2500 g], small-for-gestation birthweight [z-score ≤-1.28], large-for-gestation birthweight [z-score ≥1.28], very preterm [<32 weeks], preterm [<37 weeks], birth defects, neonatal death [0-27 days], and infant death [0-364 days of life]) were modeled by fertility status with the fertile group as reference and the subfertile group as reference, using multivariate log binomial regression and reported as adjusted risk ratios and 95% confidence intervals.Results: The study population included 459,623 women (441,420 fertile, 8054 subfertile, and 10,149 in vitro fertilization). Women in the subfertile and in vitro fertilization groups were older than their fertile counterparts. Risks for 6 of 6 pregnancy outcomes and 6 of 9 infant outcomes were increased for the subfertile group, and 5 of 6 pregnancy outcomes and 7 of 9 infant outcomes were increased for the in vitro fertilization group. For 4 of the 6 pregnancy outcomes (uterine bleeding, placental complications, prenatal hospitalizations, and primary cesarean) and 2 of the infant outcomes (low birthweight and preterm) the risk was greater in the in vitro fertilization group, with nonoverlapping confidence intervals to the subfertile group, indicating a substantially higher risk among in vitro fertilization-treated women. The highest risks for the in vitro fertilization women were uterine bleeding (adjusted risk ratio, 3.80; 95% confidence interval, 3.31-4.36) and placental complications (adjusted risk ratio, 2.81; 95% confidence interval, 2.57-3.08), and for in vitro fertilization infants, very preterm birth (adjusted risk ratio, 2.13; 95% confidence interval, 1.80-2.52), and very low birthweight (adjusted risk ratio, 2.15; 95% confidence interval, 1.80-2.56). With subfertile women as reference, risks for the in vitro fertilization group were significantly increased for uterine bleeding, placental complications, prenatal hospitalizations, primary cesarean delivery, low and very low birthweight, and preterm and very preterm birth.Conclusion: These analyses indicate that, compared with fertile women, subfertile and in vitro fertilization-treated women tend to be older, have more preexisting chronic conditions, and are at higher risk for adverse pregnancy outcomes, particularly uterine bleeding and placental complications. The greater risk in in vitro fertilization-treated women may reflect more severe infertility, more extensive underlying pathology, or other unfavorable factors not measured in this study. [ABSTRACT FROM AUTHOR]