MRI assessed placental volume and adverse pregnancy outcomes: Secondary analysis of prospective cohort study.

INTRODUCTION: Our goal was to evaluate the potential utility of magnetic resonance imaging (MRI) placental volume as an assessment of placental insufficiency. METHODS: Secondary analysis of a prospective cohort undergoing serial placental MRIs at two academic tertiary care centers. The population included 316 participants undergoing MRI up to three times throughout gestation. MRI was used to calculate placental volume in milliliters (ml). Placental-mediated adverse pregnancy outcome (cAPO) included preeclampsia with severe features, abnormal antenatal surveillance, and perinatal mortality. Serial measurements were grouped as time point 1 (TP1) <22 weeks, TP2 22 0/7-29 6/7 weeks, and TP3 ≥30 weeks. Mixed effects models compared change in placental volume across gestation between cAPO groups. Association between cAPO and placental volume was determined using logistic regression at each TP with discrimination evaluated using area under receiver operator curve (AUC). Placental volume was then added to known clinical predictive variables and evaluated with test characteristics and calibration. RESULTS: 59 (18.7 %) of 316 participants developed cAPO. Placental volume growth across gestation was slower in the cAPO group (p < 0.001). Placental volume was lower in the cAPO group at all time points, and alone was moderately predictive of cAPO at TP3 (AUC 0.756). Adding placental volume to clinical variables had moderate discrimination at all time points, with strongest test characteristics at TP3 (AUC 0.792) with sensitivity of 77.5 % and specificity of 75.3 % at a predicted probability cutoff of 15 %. DISCUSSION: MRI placental volume warrants further study for assessment of placental insufficiency, particularly later in gestation.

Treating Mild Chronic Hypertension During Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the cost effectiveness of targeting a blood pressure of less than 140/90 mm Hg compared with 160/105 mm Hg. METHODS: A decision-analytic model was constructed to compare the treatment of chronic hypertension in pregnancy at mild-range blood pressures (140/90 mm Hg) with the treatment of chronic hypertension before 20 weeks of gestation at severe-range blood pressures (160/105 mm Hg) in a theoretical cohort of 180,000 patients with mild chronic hypertension. Probabilities, costs, and utilities were derived from literature and varied in sensitivity analyses. Primary outcomes included incremental cost per quality-adjusted life-year (QALY), cases of preeclampsia, preeclampsia with severe features, severe maternal morbidity (SMM), preterm birth, maternal death, neonatal death, and neurodevelopmental delay. The cost-effectiveness threshold was $100,000 per QALY. RESULTS: Treating chronic hypertension in a population of 180,000 pregnant persons at mild-range blood pressures, compared with severe-range blood pressures, resulted in 14,177 fewer cases of preeclampsia (43,953 vs 58,130), 11,835 of which were cases of preeclampsia with severe features (40,530 vs 52,365). This led to 817 fewer cases of SMM (4,375 vs 5,192), and 18 fewer cases of maternal death (102 vs 120). Treating at a lower threshold also resulted in 8,078 fewer cases of preterm birth (22,000 vs 30,078), which led to 26 fewer neonatal deaths (276 vs 302) and 157 fewer cases of neurodevelopmental delay (661 vs 818). Overall, treating chronic hypertension at a lower threshold was a dominant strategy that resulted in decreased costs of $600 million and increased effectiveness of 12,852 QALYs. CONCLUSION: Treating chronic hypertension at a threshold of mild-range blood pressures is a dominant (lower costs, better outcomes) and cost-effective strategy that results in fewer neonatal and maternal deaths compared with the standard treatment of treating at severe range blood pressures.

Interpregnancy Interval After Stillbirth and Adverse Perinatal Outcomes.

We used a retrospective cohort of 5,581 individuals to examine the association between interpregnancy interval (IPI) after stillbirth and pregnancy outcomes of preterm birth, preeclampsia, small for gestational age, recurrent stillbirth, infant death, and neonatal intensive care unit admission in the subsequent pregnancy. The IPI was divided in six categories, with 18-23 months as referent. Association between IPI category and adverse outcomes was determined with logistic regression models adjusted for maternal race and ethnicity, age, education, insurance, and gestational age at preceding stillbirth. Adverse perinatal outcome was common in pregnancies after stillbirth, with 26.7% of individuals delivering preterm. None of the IPI categories were associated with increased risk of adverse perinatal outcomes, including the shortest category (IPI less than 3 months). This finding is meaningful for bereaved parents who desire to conceive shortly after stillbirth.

Parental Perceptions of Counseling Regarding Interpregnancy Interval after Stillbirth or Neonatal Death.

OBJECTIVE: Although guidelines exist regarding optimal interpregnancy interval (IPI) after live birth, both optimal IPI and counseling regarding recommended IPI (rIPI) after stillbirth or neonatal death is not well established. Our goal was to describe the counseling bereaved parents receive regarding IPI, parents' reactions to that counseling, and actual IPI after loss. STUDY DESIGN: Bereaved parents who had a previous pregnancy result in stillbirth or neonatal death participated in a web-based survey. Questions included demographics, details of stillbirth or neonatal death, IPI counseling, and pregnancy after loss. Demographic information, rIPI, and ac'tual IPI were reported using descriptive statistics. The Wilcoxon's rank sum test was used to test the association between rIPI and mode of delivery. The Spearman's correlation was used to test the association between rIPI and maternal age. RESULTS: A total of 275 surveys were analyzed. Mean gestational age of stillbirth delivery was 33.1 (standard deviation: 6.6) weeks. A total of 29% delivered via cesarean. Median rIPI was 6 (interquartile ratio [IQR]: 2-9) months, with the primary reason for IPI reported as the need to heal (74%). Delivery via cesarean was associated with longer rIPI, 9 versus 4.2 months (p < 0.0001). Maternal age was not associated with rIPI. Of 144 people who pursued pregnancy again, median time until attempting conception was 3.5 (IQR: 2-6) months. Median actual IPI was 6 (IQR: 4-10) months. CONCLUSION: Bereaved parents receive a wide range of counseling regarding rIPI. The majority receive rIPI and pursue actual IPI shorter than current national and international recommendations for optimal IPI. KEY POINTS: · There is variation in IPI recommendation after stillbirth/neonatal death.. · Cesarean birth is associated with longer IPI recommendation, but maternal age is not.. · Median IPI after stillbirth or neonatal death was short: 6 (IQR: 4-10) months..

Venous Thromboembolism During Pregnancy and the Postpartum Period: Risk Factors, Diagnostic Testing, and Treatment.

Importance: The risk of venous thromboembolism (VTE) increases during pregnancy and the postpartum period. Deep vein thrombosis is the most common VTE during pregnancy, but pulmonary embolism is typically of greater concern as it contributes to far higher morbidity and mortality. Diagnosis and treatment of VTE during pregnancy differ substantially from the general nonpregnant population. Objective: This review describes the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of VTE during pregnancy and the postpartum period. Evidence Acquisition: First, we reviewed the VTE guidelines from professional societies in obstetrics, cardiology, hematology, emergency medicine, pulmonology, and critical care. Second, we examined references from these documents and used PubMed to identify recent articles that cited the guidelines. Finally, we searched PubMed and Google Scholar for articles published since 2018 that included terms for pregnancy and the epidemiology, risk factors, diagnostic imaging, or treatment of VTE. Results: Venous thromboembolism risk increases throughout pregnancy and peaks shortly after delivery. More than half of pregnancy-related VTE are associated with thrombophilia; other major risks include cesarean delivery, postpartum infection, and the combination of obesity with immobilization. Most VTE can be treated with low molecular weight heparin, but cases of limb- or life-threatening VTE require consideration of thrombolysis and other reperfusion therapies. Conclusions and Relevance: Venous thromboembolism is far more frequent in antepartum and postpartum women than age-matched controls, and clinical suspicion for VTE in this population should incorporate pregnancy-specific risks. Treatment of limb- or life-threatening antepartum or postpartum VTE requires multispecialty coordination to optimize maternal and fetal outcomes.

Quantitative longitudinal T2* mapping for assessing placental function and association with adverse pregnancy outcomes across gestation.

Existing methods for evaluating in vivo placental function fail to reliably detect pregnancies at-risk for adverse outcomes prior to maternal and/or fetal morbidity. Here we report the results of a prospective dual-site longitudinal clinical study of quantitative placental T2* as measured by blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI). The objectives of this study were: 1) to quantify placental T2* at multiple time points across gestation, and its consistency across sites, and 2) to investigate the association between placental T2* and adverse outcomes. 797 successful imaging studies, at up to three time points between 11 and 38 weeks of gestation, were completed in 316 pregnancies. Outcomes were stratified into three groups: (UN) uncomplicated/normal pregnancy, (PA) primary adverse pregnancy, which included hypertensive disorders of pregnancy, birthweight <5th percentile, and/or stillbirth or fetal death, and (SA) secondary abnormal pregnancy, which included abnormal prenatal conditions not included in the PA group such as spontaneous preterm birth or fetal anomalies. Of the 316 pregnancies, 198 (62.6%) were UN, 70 (22.2%) PA, and 48 (15.2%) SA outcomes. We found that the evolution of placental T2* across gestation was well described by a sigmoid model, with T2* decreasing continuously from a high plateau level early in gestation, through an inflection point around 30 weeks, and finally approaching a second, lower plateau in late gestation. Model regression revealed significantly lower T2* in the PA group than in UN pregnancies starting at 15 weeks and continuing through 33 weeks. T2* percentiles were computed for individual scans relative to UN group regression, and z-scores and receiver operating characteristic (ROC) curves calculated for association of T2* with pregnancy outcome. Overall, differences between UN and PA groups were statistically significant across gestation, with large effect sizes in mid- and late- pregnancy. The area under the curve (AUC) for placental T2* percentile and PA pregnancy outcome was 0.71, with the strongest predictive power (AUC of 0.76) at the mid-gestation time period (20-30 weeks). Our data demonstrate that placental T2* measurements are strongly associated with pregnancy outcomes often attributed to placental insufficiency. Trial registration: ClinicalTrials.gov: NCT02749851.

DLK1: A Novel Biomarker of Placental Insufficiency in Stillbirth and Live Birth.

OBJECTIVE: Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. STUDY DESIGN: A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. RESULTS: Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB. CONCLUSION: In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB. KEY POINTS: · Maternally circulating DLK1 is correlated with placental insufficiency.. · Maternally circulating DLK1 is not correlated with SB.. · DLK1 is a promising marker for placental insufficiency..

What Matters to Whom: Patient and Public Involvement in Research.

We outline a call to action for reproductive health researchers to include patient and public involvement (PPI) in research. PPI prioritizes the patient perspective from study design through dissemination of results which centers the people research intends to serve. PPI highlights the patient as an expert in their own condition. PPI that includes groups harmed by health care disparities can draw attention to these harms and generate novel approaches to address them. Numerous frameworks exist for the use of PPI in research. Because obstetrics and gynecology conditions can be particularly sensitive, PPI is crucial in our field.

Patient-Reported Health Outcomes and Quality of Life after Peripartum Hysterectomy for Placenta Accreta Spectrum.

OBJECTIVE: Short-term morbidity of placenta accreta spectrum (PAS) is well described, but few data are available regarding long-term outcomes and quality of life. We aimed to evaluate patient-reported outcomes after hysterectomy for PAS. STUDY DESIGN: This is a prospective cohort study of women with risk factors for PAS who were enrolled antenatally. Exposed women were defined as those who underwent cesarean hysterectomy due to PAS. Unexposed women were those with three or more prior cesareans or placenta previa, but no PAS, who underwent cesarean delivery without hysterectomy. Two surveys were sent to patients at 6, 12, 24, and 36 months postpartum: (1) a general health questionnaire and (2) the SF-36, a validated quality of life survey. Aggregate scores for each questionnaire were calculated and responses were analyzed. RESULTS: At 6 months postpartum, women with PAS were more likely to report rehospitalization (odds ratio [OR] 5.83, 95% confidence interval [CI] 1.40-24.3), painful intercourse (OR 2.50, 95% CI 1.04-6.02), and anxiety/worry (OR 3.77, 95% CI 1.43-9.93), but were not statistically more likely to report additional surgeries (OR 3.39, 95% CI 0.99-11.7) or grief and depression (OR 2.45, 95% CI 0.87-6.95). At 12 months, women with PAS were more likely to report painful intercourse, grief/depression, and anxiety/worry. At 36 months, women with PAS were more likely to report grief/depression, anxiety/worry, and additional surgeries. Women with PAS reported significantly lower quality of life in physical functioning, role functioning, social functioning, and pain at 6 months postpartum, but not in other quality of life domains. Decreased quality of life was also reported at 12 and 36 months in the PAS group. CONCLUSION: Women with PAS are more likely to report ongoing long-term health issues and decreased quality of life for up to 3 years following surgery than those undergoing cesarean for other indications. KEY POINTS: · Long-term placenta accreta spectrum data to guide peripartum patient education.. · This study addresses a critical knowledge gap.. · Women affected by PAS report long-term morbidity..

Perinatal Loss: The Impact on Maternal Mental Health.

IMPORTANCE: Psychological reactions to perinatal loss, although often self-limited, may lead to significant psychological morbidities. Obstetrician-gynecologists and other maternal health providers play a key role in recognizing the range of psychological responses to perinatal loss and providing education, support, and treatment options to their patients. OBJECTIVE: This review aims to define psychological reactions associated with perinatal loss, examine psychotherapy and psychopharmacologic treatments for psychiatric morbidities, discuss interpregnancy interval following perinatal loss, and highlight brief, psychological interventions that can be implemented by maternal health providers. EVIDENCE ACQUISITION: Search terms "perinatal loss psychology," "reproductive loss grief," "perinatal psychopharmacology," "psychopharmacology grief," and "interpregnancy interval" were utilized to search PubMed, Google Scholar, and PsycINFO. RESULTS: Grief is an expected, normal response to perinatal loss. Psychological morbidities, including major depressive disorder, generalized anxiety disorder, and posttraumatic stress disorder, are also associated with perinatal loss. Risk factors for these conditions include history of a psychiatric illness, childlessness, unknown cause of perinatal loss, limited social support, and marital/relationship discord. Careful interviewing and brief screening measures can help identify patients who may suffer from depressive or anxiety disorders following reproductive loss. Patients with perinatal loss can benefit from psychological and possibly pharmacologic treatments. Recommended interpregnancy interval after perinatal loss should be customized by gestational age and cause of loss. CONCLUSIONS AND RELEVANCE: Patients with perinatal loss emotionally benefit from their reproductive health care providers acknowledging the psychological aspects of reproductive loss, inquiring about their emotional needs, and providing information regarding grief and mental health referrals.

Intrauterine Vacuum-Induced Hemorrhage-Control Device for Rapid Treatment of Postpartum Hemorrhage.

OBJECTIVE: To evaluate the effectiveness and safety of an intrauterine vacuum-induced hemorrhage-control device for postpartum hemorrhage treatment. METHODS: A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device. RESULTS: Of 107 participants enrolled with primary postpartum hemorrhage or abnormal postpartum uterine bleeding, 106 received any study treatment with the device connected to vacuum, and successful treatment was observed in 94% (100/106, 95% CI 88-98%) of these participants. In those 100 participants, definitive control of abnormal bleeding was reported in a median of 3 minutes (interquartile range 2.0-5.0) after connection to vacuum. Eight adverse events deemed possibly related to the device or procedure were reported, all of which were outlined as risks in the study and all of which resolved with treatment without serious clinical sequelae. Transfusion of 1-3 units of red blood cells was required in 35 participants, and five participants required 4 or more units of red blood cells. The majority of investigators reported the intrauterine vacuum-induced hemorrhage-control device as easy to use (98%) and would recommend it (97%). CONCLUSION: Intrauterine vacuum-induced hemorrhage control may provide a new rapid and effective treatment option for abnormal postpartum uterine bleeding or postpartum hemorrhage, with the potential to prevent severe maternal morbidity and mortality. FUNDING SOURCE: Alydia Health, Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02883673.

Family history of autoimmune disease in relation to time-to-pregnancy, pregnancy loss, and live birth rate.

Several autoimmune conditions have adverse effects on reproductive outcomes, but the relationship between family history of autoimmune disease in women without these conditions and pregnancy is uncertain. The objective of this study was to determine if there is an association between a family history of an autoimmune condition and time-to-pregnancy (TTP), pregnancy loss, and live birth. This was a prospective cohort study from a RCT of 1228 adult women ages 18-40, who were healthy, had no history of infertility, were actively attempting to conceive, and had one or two prior pregnancy losses. Of these, 1172 women had data available regarding family history of autoimmune conditions. Women with an affected first-degree relative had similar TTP when compared to those without a FHx (fecundability odds ratio 0.90, 95% confidence interval [CI] 0.70, 1.15). Women with an affected first-degree relative had a lower likelihood of live birth (relative risk [RR] 0.83, 95% CI 0.69, 0.99). Among women who achieved pregnancy, FHx of autoimmune disease was associated with a higher likelihood of pregnancy loss (RR 1.49, 95% CI 1.10, 2.03). Women who had a first-degree relative with an autoimmune disease had a similar TTP as unaffected women but a lower likelihood of live birth and higher risk of pregnancy loss. This information may encourage clinicians to evaluate women with a family history of autoimmune conditions prior to pregnancy and highlights the need for further studies to ascertain the effects of autoimmunity and pregnancy.

Umbilical Cord Abnormalities and Stillbirth.

OBJECTIVE: Umbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors. METHODS: The Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index. RESULTS: Of 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords. CONCLUSION: Umbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.

Findings in Stillbirths Associated with Placental Disease.

OBJECTIVE: Placental disease is a leading cause of stillbirth. Our purpose was to characterize stillbirths associated with placental disease. STUDY DESIGN: The Stillbirth Collaborative Research Network conducted a prospective, case-control study of stillbirths and live births from 2006 to 2008. This analysis includes 512 stillbirths with cause of death assignment and a comparison group of live births. We compared exposures between women with stillbirth due to placental disease and those due to other causes as well as between women with term (≥ 37 weeks) stillbirth due to placental disease and term live births. RESULTS: A total of 121 (23.6%) out of 512 stillbirths had a probable or possible cause of death due to placental disease by Initial Causes of Fetal Death. Characteristics were similar between stillbirths due to placental disease and other stillbirths. When comparing term live births to stillbirths due to placental disease, women with non-Hispanic black race, Hispanic ethnicity, lack of insurance, or who were born outside of the United States had higher odds of stillbirth due to placental disease. Nulliparity and antenatal bleeding also increased risk of stillbirth due to placental disease. CONCLUSION: Multiple discrete exposures were associated with stillbirth caused by placental disease. The relationship between these factors and utility of surveillance warrants further study.

Prospective Evaluation of Maternal Sleep Position Through 30 Weeks of Gestation and Adverse Pregnancy Outcomes.

OBJECTIVE: To examine the relationship between prospectively assessed maternal sleep position and subsequent adverse pregnancy outcomes. METHODS: This was a secondary analysis of a prospective observational multicenter cohort study of nulliparous women with singleton gestations who were enrolled between October 2010 and May 2014. Participants had three study visits that were not part of clinical care. They prospectively completed in-depth sleep questionnaires between 6 0/7 and 13 6/7 weeks of gestation and 22 0/7 and 29 6/7 weeks of gestation, the first and third study visits. A subset of women also underwent level 3 home sleep tests using the Embletta Gold device. The primary outcome was a composite of adverse pregnancy outcomes such as stillbirth, a small-for-gestational-age newborn, and gestational hypertensive disorders. RESULTS: A total of 8,706 (of 10,038) women had data from at least one sleep questionnaire and for pregnancy outcomes, and they comprised the population for this analysis. The primary outcome occurred in 1,903 pregnancies (22%). There was no association between reported non-left lateral or supine sleep during the last week of the first visit (adjusted odds ratio [aOR] 1.00 [95% CI 0.89-1.14]) or third visit (aOR 0.99 [95% CI 0.89-1.11] and the composite or any individual outcome, except for an apparent protective effect for stillbirth at the third visit (aOR 0.27 (95% CI 0.09-0.75). Women with objectively measured supine sleep position for at least 50% of the time were no more likely than those in the supine position 50% or less of the time to have the composite adverse outcome. CONCLUSIONS: Going to sleep in the supine or right lateral position, as self-reported before the development of pregnancy outcome and objectively assessed through 30 weeks of gestation, was not associated with an increased risk of stillbirth, a small-for-gestational-age newborn, or gestational hypertensive disorders.

The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses.

BACKGROUND: Stillbirth, defined as foetal death ≥20 weeks' gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. OBJECTIVE: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. METHODS: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. RESULTS: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. CONCLUSIONS: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

Associations Between the Features of Gross Placental Morphology and Birthweight.

The placenta plays a critical role in regulating fetal growth. Recent studies suggest that there may be sex-specific differences in placental development. The purpose of our study was to evaluate the associations between birthweight and placental morphology in models adjusted for covariates and to assess sex-specific differences in these associations. We analyzed data from the Stillbirth Collaborative Research Network's population-based case-control study conducted between 2006 and 2008, which recruited cases of stillbirth and population-based controls in 5 states. Our analysis was restricted to singleton live births with a placental examination (n = 1229). Characteristics of placental morphology evaluated include thickness, surface area, difference in diameters, shape, and umbilical cord insertion site. We used linear regression to model birthweight as a function of placental morphology and covariates. Surface area had the greatest association with birthweight; a reduction in surface area of 83 cm2, which reflects the interquartile range, is associated with a 260.2-g reduction in birthweight (95% confidence interval, -299.9 to -220.6), after adjustment for other features of placental morphology and covariates. Reduced placental thickness was also associated with lower birthweight. These associations did not differ between males and females. Our results suggest that reduced placental thickness and surface area are independently associated with lower birthweight and that these relationships are not related to sex.

Associations Between Features of Placental Morphology and Birth Weight in Dichorionic Twins.

Low birth weight is associated with perinatal and long-term morbidity and mortality, and may be a result of abnormal placental development and function. In studies of singletons, associations have been reported between features of placental morphology and birth weight. Evaluating similar associations within twin pairs offers a unique opportunity to control for key confounders shared within a twin pair, including gestational age, parental characteristics, and intrauterine environment. Data from 3 studies in the United States that were completed from 2012 to 2013, 2006 to 2008, and 1959 to 1966 were used in our analysis of 208 sets of dichorionic twins with unfused placentas. We used linear regression to model difference in birth weight within a twin pair as a function of differences in placental characteristics (i.e., thickness, 2-dimensional surface area, intraplacental difference in diameter). After controlling for sex discordance, a 75.3- cm2 difference in placental surface area, which reflects the interquartile range, was associated with a difference in birth weight of 142.1 g (95% confidence interval (CI): 62.9, 221.3). The magnitude of the association also may be larger for same-sex male pairs than same-sex female pairs (males: 265.8 g, 95% CI: 60.8, 470.8; females: 133.0 g, 95% CI: 15.7, 250.3). Strong associations between surface area and birth weight are consistent with reported results for singleton pregnancies.

Acute effects of air pollutants on spontaneous pregnancy loss: a case-crossover study.

OBJECTIVE: To investigate the relationship between acute exposure to air pollutants and spontaneous pregnancy loss. DESIGN: Case-crossover study from 2007 to 2015. SETTING: An academic emergency department in the Wasatch Front area of Utah. PATIENT(S): A total of 1,398 women who experienced spontaneous pregnancy loss events. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Odds of spontaneous pregnancy loss. RESULT(S): We found that a 10-ppb increase in 7-day average levels of nitrogen dioxide was associated with a 16% increase in the odds of spontaneous pregnancy loss (odds ratio [OR] = 1.16; 95% confidence interval [CI] 1.01-1.33; P=.04). A 10-µg/m3 increase in 3-day and 7-day averages of fine particulate matter were associated with increased risk of spontaneous pregnancy loss, but the associations did not reach statistical significance (OR3-day average = 1.09; 95% CI 0.99-1.20; P=.05) (OR7-day average = 1.11; 95% CI 0.99-1.24; P=.06). We found no evidence of increased risk for any other metrics of nitrogen dioxide or fine particulate matter or any metric for ozone. CONCLUSIONS: We found that short-term exposure to elevated levels of air pollutants was associated with higher risk for spontaneous pregnancy loss.