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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 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

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.

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.

Intrauterine vacuum-induced hemorrhage control may provide an effective treatment option for postpartum hemorrhage that has the potential to prevent severe maternal morbidity and mortality., 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.

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..

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.

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., Highlights • Some autoimmune conditions may negatively impact reproductive health. • Autoimmune disease can cluster in families highlighting relevance of family history. • Women with family history of autoimmunity had higher risk of pregnancy loss. • Results suggest possible shared mechanism of miscarriage and predisposition to autoimmunity. • Family history may be important for understanding risk factors for pregnancy loss.

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- cm(2) 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.

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.

Background Obstetric delivery is among the most common in-hospital procedures experienced by reproductive-age women, yet there is little literature on patterns of postpartum opioid prescriptions after such episodes. Methods We used claims data from 871,195 vaginal deliveries to 768,455 privately-insured women with an in-hospital delivery between June 2001 and July 2013 to examine the state- and census division-level proportions of women who filled an opioid prescription within four days of hospital discharge after vaginal delivery. Our primary outcome examined the proportion of women who filled an opioid prescription after uncomplicated vaginal delivery (e.g., without forceps extraction, vacuum extraction, or 3rd/4th degree perineal laceration). Secondary outcomes examined state- and census division-level variation in opioid prescription duration (proportion of prescriptions exceeding five days) and dose (proportion of prescriptions exceeding 280 morphine milligram equivalents). We also displayed national temporal trends in opioid prescribing rate and dose for uncomplicated vaginal delivery in comparison to complicated vaginal delivery. Results Across states, we found a 7-fold variation in postpartum opioid prescription rates (7.6–53.4%), a 5-fold variation in opioid prescriptions for greater than five days' duration (5.1–25.7%), and a 19% absolute difference in opioid prescriptions for greater than 280 morphine milligram equivalents (0–19.3%) following uncomplicated vaginal delivery. Conclusions These wide variations in postpartum opioid prescription practices suggest opportunities to develop guidelines on postpartum opioid use, to improve prescription safety, and to reduce opioid-related harms among women in the postpartum period.

Hypertensive disease of pregnancy (HDP) with placental insufficiency is the most common cause of fetal growth restriction (FGR) in the developed world. Despite the known negative consequences of HDP both to the mother and fetus, little is known about the longitudinal placental changes that occur as HDP progresses in pregnancy. This is because longitudinal sampling of human placentae during each gestation is impossible. Therefore, using a mouse model of thromboxane A2-analog infusion to mimic human HDP in the last trimester, we calculated placental efficiencies based on fetal and placental weights; quantified spongiotrophoblast and labyrinth thicknesses and vascular density within these layers; examined whether hypoxia signaling pathway involving vascular endothelial growth factor A (VEGFA) and its receptors (VEGFR1, VEGFR2) and matrix metalloproteinases (MMPs) contributed to vascular change; and examined nutrient transporter abundance including glucose transporters 1 and 3 (GLUT1, GLUT3), neutral amino acid transporters 1, 2, and 4 (SNAT1, SNAT2, and SNAT4), fatty acid transporters 2 and 4 (FATP2, FATP4), and fatty acid translocase (CD36) from embryonic day 15.5 to 19 in a 20-day C57Bl/6J mouse gestation. We conclude that early-to-mid gestation hypertensive placentae show compensatory mechanisms to preserve fetal growth by increasing placental efficiencies and maintaining abundance of important nutrient transporters. As placental vascular network diminishes over late hypertension, placental efficiency diminishes and fetal growth fails. Neither hypoxia signaling pathway nor MMPs mediated the vascular diminution in thismodel. Hypertensive placentae surprisingly exhibit a sex-differential expression of nutrient transporters in late gestation despite showing fetal growth failure in both sexes.Summary SentenceExcess thromboxane A2 leads to a mouse phenotype of hypertensive disease of pregnancy and fetal growth restriction with evidence of altered placental vascular development and nutrient transporter abundance.

OBJECTIVE: Placenta previa is associated with maternal hemorrhage, but most literature focuses on morbidity in the setting of placenta accreta. We aim to characterize maternal morbidity associated with previa and to define risk factors for hemorrhage. METHODS: This is a secondary cohort analysis of the NICHD Maternal-Fetal Medicine Units Network Cesarean Section Registry. This analysis included all women undergoing primary Cesarean delivery without placenta accreta. 496 women with previa were compared to 24,201 women without previa. Primary outcome was composite maternal hemorrhagic morbidity. Non-hemorrhagic morbidities and risk factors for hemorrhage were also evaluated. RESULTS: Maternal hemorrhagic morbidity was more common in women with previa (19 vs 7%, aRR 2.6, 95% CI 1.9-3.5). Atony requiring uterotonics (aRR 3.1, 95% CI 2.0-4.9), red blood cell transfusion (aRR 3.8, 95% CI 2.5-5.7), and hysterectomy (aRR 5.1, 95% CI 1.5-17.3) were also more common with previa. For women with previa, factors associated with maternal hemorrhage were pre-delivery anemia, thrombocytopenia, diabetes, magnesium use, and general anesthesia. CONCLUSION: Placenta previa is an independent risk factor for maternal hemorrhagic morbidity. Some risk factors are modifiable, but many are intrinsic to the clinical scenario.

To examine the relationship between prospectively assessed maternal sleep position and subsequent adverse pregnancy outcomes.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.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.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.

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.

Background: Maternal sleep position on the back or right side has been associated with adverse pregnancy outcomes, leading to recommendations to always sleep on the left side and maternal anxiety about sleep. However, available data are from case-control studies, which are subject to recall bias. Our objective was to examine the relationship between prospectively assessed 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. Participants prospectively completed in-depth sleep questionnaires between 6+0 and 13+6 week's gestation (V1) and 22+0 and 29+6 week's gestation (V3). At each visit, women were asked in what position they went to sleep last night and on average during the past week. 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 including stillbirth, small for gestational age fetus (SGA), and gestational hypertensive disorders. Results: 8,706 (of 10,038 total) women had data from at least one sleep questionnaire and for pregnancy outcomes, and they comprised the population for this analysis. There was no association between reported non-left lateral or supine sleep during the last week at V1 or V3 and the composite or any individual outcome, except for an apparent protective effect for stillbirth at V3. Women with objectively measured supine sleep position for > 50% of the time were no more likely than those in the supine position ≤ 50% of the time to have the composite adverse outcome. Conclusions: Going to sleep in the supine or right lateral position, as self reported prior to the development of pregnancy outcome and objectively assessed through 30 weeks gestation was not associated with an increased risk of stillbirth, SGA fetus or gestational hypertensive disorders. Trial Registration: clinicaltrials.gov (NCT01322529) Funding Statement: This study is supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD063036, RTI International; U10 HD063072, Case Western Reserve University; U10 HD063047, Columbia University; U10 HD063037, Indiana University; U10 HD063041, University of Pittsburgh; U10 HD063020, Northwestern University; U10 HD063046, University of California Irvine; U10 HD063048, University of Pennsylvania; and U10 HD063053, University of Utah. In addition, support was provided by respective Clinical and Translational Science Institutes to Indiana University (UL1TR001108) and University of California Irvine (UL1TR000153). Declaration of Interests: No conflicts of interest to declare or report. Ethics Approval Statement: The study was approved by the Institutional Review Boards at each clinical site and the Data Coordinating Center, and all participants gave written informed consent.

In the literature, there is growing evidence that assisted reproductive techniques increase the risk of pregnancy complications in subfertile couples. Moreover, many concomitant preconception risk factors for subfertility are frequently present in the same subject and increase the risk of pregnancy complications. This review aimed to summarize in a systematic fashion the best current evidence regarding the effects of preconception maternal factors on maternal and neonatal outcomes. A literature search up to March 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar. An evidence-based hierarchy was used to determine which articles to include and analyse. Available data show that the risk of pregnancy complications in spontaneous and assisted conceptions is likely multifactorial, and the magnitude of this risk is probably very different according specific subgroups of patients. Notwithstanding the only moderate level and quality of the available evidence, available data suggest that the presence and the treatment of specific preconception cofactors of subfertility should be always taken into account both in clinical practice and for scientific purposes.

Choosing an evidence-based workup and treatment for recurrent pregnancy loss is imperative to provide best patient care and create a culture that permits rigorous research into potential (not yet evidence-based) tests and therapeutics. As health sciences technologies become more sophisticated, more precise, and less expensive, new tools may be developed that allow better evaluation and treatment of couples with recurrent pregnancy loss. The goal must remain optimizing value and adhering to evidence-based care.

Introduction Stillbirth, preeclampsia, and gestational hypertension (PE/GH) have similar clinical risk factors and redundant placental pathology. We aim to discern if stillbirth with PE/GH has a particular phenotype by comparing stillbirths with and without PE/GH. Methods Secondary analysis of the Stillbirth Collaborative Research Network, a population-based cohort study of all stillbirths and a sample of live births from 2006 to 2008 in five catchment areas. We compared placental pathology between stillbirths and with and without PE/GH, stratified by term or preterm. We also compared placental pathology between stillbirths and live births with PE/GH. Results 79/518 stillbirths and 140/1200 live births had PE/GH. Amongst preterm stillbirths, there was higher feto-placental ratio in PE/GH pregnancies (OR 1.24 [1.11, 1.37] per unit increase), and there were more parenchymal infarctions (OR 5.77 [3.18, 10.47]). Among PE/GH pregnancies, stillbirths had increased maternal and fetal vascular lesions, including retroplacental hematoma, parenchymal infarction, fibrin deposition, fetal vascular thrombi, and avascular villi. Discussion Stillbirth pregnancies are overwhelmingly associated with placental lesions. Parenchymal infarctions are more common in PE/GH preterm stillbirths, but there is significant overlap in lesions found in stillbirths and PE/GH.

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.

Objective Preterm delivery for preeclampsia or placental insufficiency (PREPI) is a clinical criterion for antiphospholipid syndrome (APS), but no prior prospective studies have used the international classification criteria for APS. Our objective is to determine the proportion of women with PREPI who test positive for aPL using international criteria for antiphospholipid antibody (aPL) assays. Methods We conducted a prospective, case-control study of 148 women delivered Results Controls were more likely to be Caucasian (87% vs 70%, p = 0.006) and had lower BMIs (BMI 26 vs 33, p Conclusion Women requiring early delivery for PREPI are more likely to have aPL (and thus APS) than controls. This is the first prospective study using both obstetric definitions and laboratory criteria in accordance with APS international criteria.

BACKGROUND Physician satisfaction is linked to positive patient outcomes. Mothers form an increasing fraction of the obstetrics and gynecology (ob/gyn) workforce. OBJECTIVE Define factors that affect physician satisfaction among ob/gyn physicians who are also mothers. METHODS We constructed and validated a Redcap survey and invited members of online ob/gyn-mom groups to participate. Characteristics of participants' professional and personal lives were evaluated for possible association with the satisfaction outcomes. Comparison testing was performed using Chi-squared test or Fisher's exact test for categorical variables, Student's t-test for parametric variables, and Wilcoxon Rank-Sum test for non-parametric variables. RESULTS Responses were received from 232 participants. A majority reported being unsatisfied with their time to spend with children (66%), partner (70%), and on personal hobbies/activites (75%). Eighty-percent rate professional morale as very/somewhat positive. Women who rated their morale as very/somewhat positive worked fewer hours per week than women with neutral/negative responses (43.6 vs 49.7, p = 0.01). Women with positive morale were also less likely to work over 50 h/week (39.5% vs 56.8%, p = 0.04). CONCLUSIONS Ob/gyn physician-mothers have high professional morale but are dissatisfied with time for extra-professional activities. Longer clinical hours correlate with dissatisfaction based on several measurements.

Objectives To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose aspirin. Preconception anticardiolipin (aCL) and anti-β2-glycoprotein-I (a-β2-I) were assessed in 1208 women with one or two prior pregnancy losses and no more than two prior live births. Comparison cohorts were defined by positive aPL (+aPL) or negative aPL (–aPL) status. All women were followed for six menstrual cycles while trying to conceive; if successful, they underwent an ultrasound at 6–7 weeks’ gestation. EPL was defined as loss prior to 10 weeks’ gestation; embryonic loss was loss after visualization of an embryo but prior to 10 weeks; clinical loss was any loss after visualization of an embryo (with or without fetal cardiac activity detected). Results In total, 14/1208 (1%) tested positive for +aPL. 786/1208 (65%) women had positive human chorionic gonadotropin during the study period, of which 9/786 (1%) had +aPL. Of the 786 pregnant women, 589 (75%) had live births and 24% had pregnancy losses. Women with +aPL experienced EPL at similar rates as women with –aPL, 44% vs 21% (aRR 2.4, 95% confidence interval (CI) 0.5–10.9). Embryonic loss was more common in women with +aCL IgM (aRR 4.8, 95% CI 1.0–23.0) and in women with two positive aPL. Clinical pregnancy loss was more common in women with positive a-β2-I IgM (50% vs 16.5%, aRR 3.7, 95% CI 1.3–10.8). Conclusion Positive levels of aPL are rare in women with one or two prior pregnancy losses and are not clearly associated with an increased rate of subsequent loss. Clinical trial registration The original source study was registered at ClinicalTrials.gov (#NCT00467363).

Objective Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a defect in cholesterol biosynthesis with mutations in 7-dehydrocholesterol reductase (DHCR7). A total of 3% of Caucasians carry DHCR7 mutations, theoretically resulting in a homozygote frequency of 1/4000. However, SLOS occurs in only 1/20,000 to 60,000 live births. Our objective was to assess DHCR7 mutations in unexplained stillbirths. Study Design Prospective, multicenter, population-based case–control study of all stillbirths and a representative sample of live births enrolled in five geographic areas. Cases with stillbirth due to obstetric complications, infection, or aneuploidy, and those with poor quality deoxyribonucleic acid (DNA) were excluded. DNA was extracted from placental tissue stored at –80°C, and exons 3 to 9 of the DCHR7 gene were amplified, purified, and subjected to bidirectional sequencing to identify mutations. Results One-hundred forty four stillbirths were unexplained and had adequate DNA for analysis. Nine stillbirths of 139 (6.5%) had a single mutation in one allele in coding exons 3 to 9 of DHCR7 (Table 1). One case (0.7%) was a compound heterozygote for mutations in exons 3 to 9 of DHCR7; this fetus had no clinical or histologic features of SLOS. Conclusion We detected SLOS mutations in only 0.7% of stillbirths. This does not support a strong association between unrecognized DHCR7 mutations and stillbirth.

Objective To estimate the proportion of potentially preventable stillbirths in the United States. Methods We conducted a secondary analysis of 512 stillbirths with complete evaluation enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based case-control study of stillbirth in the United States. Cases of stillbirth underwent standard evaluation that included maternal interview, medical record abstraction, biospecimen collection, postmortem examination, placental pathology, and clinically recommended evaluation. Each stillbirth was assigned probable and possible causes of death using the Initial Causes of Fetal Death algorithm system. For this analysis, we defined potentially preventable stillbirths as those occurring in nonanomalous fetuses, 24 weeks of gestation or greater, and weighing 500 g or greater that were 1) intrapartum, 2) the result of medical complications, 3) the result of placental insufficiency, 4) multiple gestation (excluding twin-twin transfusion), 5) the result of spontaneous preterm birth, or 6) the result of hypertensive disorders of pregnancy. Results Of the 512 stillbirths included in our cohort, causes of potentially preventable stillbirth included placental insufficiency (65 [12.7%]), medical complications of pregnancy (31 [6.1%]), hypertensive disorders of pregnancy (20 [3.9%]), preterm labor (16 [3.1%]), intrapartum (nine [1.8%]), and multiple gestations (four [0.8%]). Twenty-seven stillbirths fit two or more categories, leaving 114 (22.3%) potentially preventable stillbirths. Conclusion Based on our definition, almost one fourth of stillbirths are potentially preventable. Given the predominance of placental insufficiency among stillbirths, identification and management of placental insufficiency may have the most immediate effect on stillbirth reduction.

Antiphospholipid syndrome is a pro-thrombotic, pro-inflammatory condition defined by at least one clinical criterion and one laboratory finding. Clinical criteria are met by history of thrombosis or obstetric morbidity, including recurrent early pregnancy loss, fetal death, or delivery prior to 34 weeks gestation due to pre-eclampsia or placental insufficiency. Laboratory criteria are evidence of lupus anticoagulant or high titers of anticardiolipin or anti-β2-glycoprotein-I IgG or IgM. Treatment during pregnancy is primarily based on anticoagulant therapy, either at prophylactic or therapeutic doses depending on thrombosis history. This treatment certainly reduces thrombosis risk and may also improve obstetric outcome.

Low technology interventions for fertility enhancement (LTIFE) are strategies that avoid retrieval, handling, and manipulation of female gametes. The definition of LTIFE is yet to be widely accepted and clarified, but they are commonly used in milder cases of infertility and subfertility. Based on these considerations, the aim of the present study was comprehensively to review and investigate the obstetric and perinatal outcomes in subfertile patients who underwent LTIFE.A literature search up to May 2017 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science, and Google Scholar. An evidence-based hierarchy was used according to The Oxford Centre for Evidence-Based Medicine to determine which articles to include and analyze, and to provide a level of evidence of each association between intervention and outcome.This analysis identified preliminary and low-grade evidence on the influence of LTIFE on obstetric and perinatal outcomes in subfertile women.LTIFE women should deserve major consideration from Clinicians/Researchers of Reproductive Medicine, because these treatments could be potentially responsible for mothers' and babies' complications. So far, the lack of well-designed and unbiased studies makes further conclusions difficult to be drawn.

Clinical trials support the efficacy and safety of magnesium sulfate for cerebral palsy prevention. We evaluated the implementation of a clinical protocol for the use of magnesium for cerebral palsy prevention in our large women's hospital, focusing on uptake, indications, and safety.We performed a review of selected gravidas with threatened or planned delivery before 32 weeks of gestation from October 2007 to February 2011. The primary study outcome was the change in the rate of predelivery administration of magnesium sulfate over this time period.Three hundred seventy-three patients were included. In 2007, before guideline implementation, 20% of eligible gravidas (95% confidence interval [CI] 9.1-35.6%) received magnesium before delivery compared with 93.9% (95% CI 79.8-99.3%) in the final 2 months of the study period (P.001). Dosing did not vary significantly over the 4 study years: the median number of treatments was one, the total predelivery median dose ranged from 15 to 48 g, and the median duration of therapy ranged from 3 to 12 hours. After 3 years, magnesium administration was almost universal among patients diagnosed with preeclampsia, preterm labor, or preterm premature rupture of membranes (95.4%), whereas patients delivered preterm for fetal growth restriction were significantly less likely to receive predelivery magnesium (44%, P.001). No maternal or perinatal magnesium-attributable morbidity was noted. Among patients eligible for the protocol who received magnesium, 84.2% delivered before 32 weeks of gestation.It is feasible to implement a magnesium sulfate cerebral palsy prevention protocol into clinical practice.III.

The presence of antiphospholipid antibodies is considered a risk factor for pre-eclampsia. Two meta-analyses and a number of case-control and cohort studies have found associations between pre-eclampsia and lupus anticoagulant, anticardiolipin, and/or anti-β2 glycoprotein I. However, existing literature is inconsistent, with varying severity of pre-eclampsia phenotype examined, differing aPL titer cutoffs used to define positive status, and an overwhelming lack of repeat confirmatory aPL testing. This calls into question the link between aPLs and pre-eclampsia, or at least makes it less well defined. There is evidence for a mechanistic pathway between aPLs and adverse pregnancy outcomes (APOs) including pre-eclampsia via the complement pathway. Complement appears to be overactive in pregnancies affected by APOs. A mouse model has show that the fetal wastage caused by treatment with human aPLs can be salvaged by either creating genetic knockouts along the complement, TNF-alpha, and tissue factor pathways or be treating mice with monoclonal antibodies blocking key complement factors. Thus, this is worth further investigation to clarify the likely association of aPLs and pre-eclampsia in humans, as well is to further evaluate the interaction with complement in human pregnancies.