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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]

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]

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]

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]

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]

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]

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]

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]

Objective: The objective of the study was to examine the relationship between sleep-disordered breathing (SDB) and adverse pregnancy outcomes in a high-risk cohort. Study Design: This was a planned analysis of a prospective cohort designed to estimate the prevalence and trends of SDB in high-risk pregnant women. We recruited women with a body mass index of 30 kg/m2 or greater, chronic hypertension, pregestational diabetes, prior preeclampsia, and/or a twin gestation. Objective assessment of SDB was completed between 6 and 20 weeks and again in the third trimester. SDB was defined as an apnea hypopnea index of 5 or greater and further grouped into severity categories: mild SDB (5-14.9), moderate SDB (15-29.9), and severe SDB (≥30). Pregnancy outcomes (preeclampsia, gestational diabetes, preterm birth, infant weight) were abstracted by physicians blinded to the SDB results. Results: Of the 188 women with a valid early pregnancy sleep study, 182 had complete delivery records. There was no relationship demonstrated between SDB exposure in early or late pregnancy and preeclampsia, preterm birth less than 34 weeks, and small-for-gestational-age (<5%), or large-for-gestational-age (>95%) neonates. Conversely, SDB severity in early pregnancy was associated with the risk of developing gestational diabetes (no SDB, 25%; mild SDB, 43%; moderate/severe SDB, 63%; P = .03). The adjusted odds ratio for developing gestational diabetes for moderate/severe SDB was 3.6 (0.6, 21.8). Conclusion: This study suggests a dose-dependent relationship between SDB in early pregnancy and the subsequent development of gestational diabetes. In contrast, no relationships between SDB during pregnancy and preeclampsia, preterm birth, and extremes of birthweight were demonstrated. [Copyright &y& Elsevier]

Objective: To assess angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes, and their predictive accuracy. Study Design: This cohort study measured serum Ang-1 and Ang-2 levels in 4785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks, and stillbirth). Results: Median (interquartile range) levels for Ang-1, Ang-2, and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/mL (13.6–26.4), 15.5 ng/mL (10.3–22.7), and 1.21 (0.83–1.73), respectively. Maternal age, weight, country of birth, and socioeconomic status significantly affected Ang-1, Ang-2, and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (<10th percentile) and high Ang-1/Ang-2 ratio (>90th percentile) had increased risk of developing most adverse pregnancy outcomes. Compared with the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage (Ang-1/Ang-2 ratio area under receiver operating characteristic curve = 0.70; maternal risk factors = 0.58). Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes. Conclusion: Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information. [Copyright &y& Elsevier]

Objective: Symptoms of sleep-disordered breathing (SDB) are increased in pregnancy compared to the nongravid state. Maternal SDB may be associated with adverse pregnancy outcomes, but this is still under investigation. We performed a systematic literature review, and where feasible, a metaanalysis, to evaluate whether women with SDB in pregnancy have a higher risk of specific adverse pregnancy outcomes compared with women without SDB. Study Design: Original studies published until June 2012 evaluating the association between gestational hypertension/preeclampsia, gestational diabetes, low birthweight infants, and maternal SDB, defined either by symptoms or the reference standard polysomnography, were identified from PubMed, EMBASE, and Web of Science. Data were extracted on study design and outcome estimates. When appropriate, effect estimates from each study were pooled using a random-effects model. Results: Of the 4386 studies identified, 31 met the defined criteria. Twenty-one studies, all observational in design, reported dichotomous outcomes; 9 of these adjusted for potential confounders. Maternal SDB was significantly associated with gestational hypertension/preeclampsia (pooled adjusted odds ratio [aOR], 2.34; 95% confidence interval [CI], 1.60–3.09; 5 studies), and gestational diabetes (pooled aOR, 1.86; 95% CI, 1.30–2.42; 5 studies). Conclusion: Based on published observational studies to date, maternal SDB is associated with an increased risk of gestational hypertension and gestational diabetes after adjusting for potential confounders. However, large-scale, prospective cohort, and interventional studies are needed to further elucidate the relationship between maternal SDB and adverse pregnancy outcomes. [Copyright &y& Elsevier]

Objective: We sought to estimate the association between maternal seizure disorder and adverse pregnancy outcomes. Study Design: We performed a retrospective cohort study of singleton, nonanomalous pregnancies. Women with self-reported seizure disorder were compared to women without medical problems. The primary outcome was intrauterine growth restriction (IUGR) <10th percentile. Secondary outcomes included IUGR <5th percentile, stillbirth, preeclampsia, and preterm delivery. A sensitivity analysis was performed using women who reported using antiepileptics to estimate the impact of disease severity on pregnancy outcomes. Results: Of 47,118 women, 440 reported a seizure disorder. Women with seizure disorder were not at increased risk of IUGR <10th percentile (adjusted odds ratio, 1.11; 95% confidence interval, 0.82–1.50), IUGR <5th percentile, stillbirth, preeclampsia, or preterm delivery. The results were similar in the sensitivity analysis of women taking antiseizure medications. Conclusion: Our results suggest women with a seizure disorder are not at increased risk of IUGR, stillbirth, preeclampsia, or preterm delivery. [ABSTRACT FROM AUTHOR]

Objective: We sought to estimate the risks of adverse pregnancy outcomes associated with early vaginal bleeding in twin pregnancies. Study Design: In a retrospective cohort study of consecutive twin pregnancies undergoing anatomic survey, we compared women who reported vaginal bleeding at <22 weeks to those who did not. Exclusion criteria included monoamniotic pregnancies, twin-to-twin transfusion syndrome, and placenta previa. Primary outcomes included preeclampsia, abruption, preterm premature rupture of membranes (PPROM), preterm birth <34 weeks, and intrauterine growth restriction. Results: Of 2106 pregnancies meeting inclusion criteria, 175 reported vaginal bleeding. Twin pregnancies with early vaginal bleeding had significantly higher risks of abruption, PPROM, and preterm birth compared to twin pregnancies without bleeding. The findings were similar when twin pairs were stratified by parity or maternal comorbidities. Conclusion: Twin pregnancies complicated by vaginal bleeding in early pregnancy have an increased risk of abruption, PPROM, and preterm birth <34 weeks. [ABSTRACT FROM AUTHOR]

Objective: We sought to estimate whether the presence of a maternal uterine anomaly is associated with adverse pregnancy outcomes. Study Design: This retrospective cohort study included singleton pregnancies undergoing routine anatomic survey from 1990 through 2008 at a major tertiary care medical center. Pregnancies with a diagnosis of uterine anomaly (uterine septum, unicornuate uterus, bicornuate uterus, uterine didelphys) were compared to those with normal anatomy. Primary outcomes of interest were spontaneous preterm birth (PTB), breech presentation, and cesarean delivery. Results: The presence of an anomaly was associated with PTB <34 weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI], 4.8–11.4; P < .01), PTB <37 weeks (aOR, 5.9, 95% CI, 4.3–8.1; P < .01), primary nonbreech cesarean delivery (aOR, 2.6; 95% CI, 1.7–4.0; P < .01), preterm premature rupture of membranes (aOR, 3.2; 95% CI, 1.8–5.6; P < .01), and breech presentation (aOR, 8.6; 95% CI, 6.2–12.0; P < .01). Conclusion: Women with a uterine anomaly are at risk for PTB, highlighting an at-risk population that needs additional study for possible interventions for PTB prevention. [ABSTRACT FROM AUTHOR]