PCOS and the risk of pre-eclampsia.

RESEARCH QUESTION: What is the association between polycystic ovary syndrome (PCOS) and pre-eclampsia? Data suggest that patients with PCOS are at increased risk of developing pre-eclampsia; however, several studies have not found an independent association between the two. DESIGN: A retrospective case-control study of singleton deliveries at a tertiary care hospital from 2011 to 2015. Patients with pre-eclampsia (cases) were matched to the next delivery without pre-eclampsia (controls) on gestational age week. Medical history data, a diagnosis or clinical features of PCOS and obstetric data, including pre-eclampsia, were abstracted from the medical record. Groups were compared with the chi-squared test, and conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). OR were adjusted for maternal age at delivery and race/ethnicity. RESULTS: This study included 435 cases and 435 controls. Cases were more likely to be Black compared with controls. Age, comorbidities, features of PCOS and use of IVF were similar between groups. Patients with pre-eclampsia were not more likely to have PCOS (8.3%) than those without pre-eclampsia (6.2%, adjusted OR 1.40, 95% CI 0.81-2.30). Sensitivity analyses for body mass index and parity suggested an increased pre-eclampsia risk for patients with PCOS and these additional factors, however no group showed a statistically significant association between PCOS and pre-eclampsia. CONCLUSIONS: In this study, a history of PCOS was not associated with the risk of pre-eclampsia. Further investigation is necessary to determine whether there are subgroups of PCOS patients who are at increased risk of pre-eclampsia.

A Review of the Neurosurgical Management of Brain Metastases During Pregnancy.

OBJECTIVE: Patients with pregnancy-associated secondary brain tumors (PASBT) are challenging to manage. Because no guidelines for the management of such patients currently exist, we performed a systematic review of the literature using PRISMA guidelines with a discussion of management from a neurosurgeon's perspective. METHOD: Systematic review of the literature using PRISMA guidelines from 1999 to 2018. RESULTS: We identified 301 studies of which 16 publications (22 patients reporting 25 pregnancies, 20 deliveries, 5 early terminations) were suitable for final analysis. The most frequent primary cancers were breast (8/22, 36.36%), skin (6/22, 27.27%), and lung (5/22, 22.73%). Four patients (18.18%) had neurosurgical procedures during their pregnancies. Five patients (22.73%) received neurosurgical resection after their pregnancies. Nine patients (40.91%) received radiation therapy and seven patients (31.82%) received chemotherapy during pregnancy while seven patients (31.82%) received chemotherapy and radiation after pregnancy. There was 1 fetal death (5%) out of 20 healthy deliveries. Five pregnancies (20%) were terminated in the first trimester due to a need for urgent neurosurgical intervention. CONCLUSION: Management of PASBT remains a challenging issue. Maternal and fetal risks associated with surgical resection and teratogenicity due to adjuvant therapy should be discussed in the context of a multidisciplinary team. Timing of surgery and the use of systemic chemoradiation depends on the gestational age (GA) of the fetus, extent, and control of the mother's primary and metastatic disease. Guidelines need to be established to help neuro-oncology teams safely and effectively manage this group of patients.

Outcomes of prenatally diagnosed spontaneous chorioamniotic membrane separation in singleton pregnancies: A systematic review of case series and case reports.

OBJECTIVES: To provide an overview of perinatal outcomes in prenatally diagnosed spontaneous chorioamniotic separation (sCAS). METHODS: A systematic search of the literature was performed from inception to July 2019, including PubMed, Ovid MEDLINE, and Ovid EMBASE. All studies reporting prenatally diagnosed sCAS after 16 weeks' gestation in singleton pregnancies were eligible. Two independent reviewers used standardized forms for data abstraction. RESULTS: Of 408 screened abstracts, 17 studies reporting 118 cases of sCAS were included. Among 113 cases with delivery outcomes, preterm birth (PTB) occurred in 60 (53.1%, 95% confidence interval [CI] 43.9-62.3%). Intrauterine fetal demise (IUFD) occurred in seven (6.2%, 95% CI 1.8-10.6%) cases, with four due to cord strangulation. Spontaneous abortion occurred in one (0.88%, 95% CI -0.84-2.6%) case. Among 104 cases with postnatal follow-up, there were six (5.8%, 95% CI 1.3-10.3%) neonatal deaths and one (0.96%, 95% CI -0.91-2.8%) infant death. Perinatal mortality (IUFD and neonatal deaths) was 11.0% (95% CI 5.4-16.7%). CONCLUSIONS: sCAS may be associated with increased risk of PTB, however, the available data are largely case reports and series. Antepartum surveillance after viability can be considered due to risk of cord accidents. Prospective study is necessary to understand the clinical implications of sCAS.

Chiari I malformation and pregnancy: a comprehensive review of the literature to address common questions and to guide management.

BACKGROUND: The optimal management of Chiari I malformation during pregnancy remains uncertain. Labor contractions, which increase intracranial pressure, and neuraxial anesthesia both carry the theoretical risk of brainstem herniation given the altered CSF dynamics inherent to the condition. Mode of delivery and planned anesthesia, therefore, require forethought to avoid potentially life-threatening complications. Since the assumed potential risks are significant, we seek to systematically review published literature regarding Chiari I malformation in pregnancy and, therefore, to establish a best practice recommendation based on available evidence. METHODS: The English-language literature was systematically reviewed from 1991 to 2018 according to PRISMA guidelines to assess all pregnancies reported in patients with Chiari I malformation. After analysis, a total of 34 patients and 35 deliveries were included in this investigation. Additionally, a single case from our institutional experience is presented for illustrative purposes but not included in the statistical analysis. RESULTS: No instances of brain herniation during pregnancy in patients with Chiari I malformation were reported. Cesarean deliveries (51%) and vaginal deliveries (49%) under neuraxial blockade and general anesthesia were both reported as safe and suitable modes of delivery. Across all publications, only one patient experienced a worsening of neurologic symptoms, which was only later discovered to be the result of a previously undiagnosed Chiari I malformation. Several patients underwent decompressive suboccipital craniectomy to treat the Chiari I malformation during the preconception period (31%), during pregnancy (3%), and after birth (6%). Specific data regarding maternal management were not reported for a large number (21) of these patients (60%). Aside from one abortion in our own institutional experience, there was no report of any therapeutic abortion or of adverse fetal outcome. CONCLUSIONS: Although devastating maternal complications are frequently feared, very few adverse outcomes have ever been reported in pregnant patients with a Chiari I malformation. The available evidence is, however, rather limited. Based on our survey of available data, we recommend vaginal delivery under neuraxial blockade for truly asymptomatic patients. Furthermore, based on our own experience and physiological conceptual considerations, we recommend limiting maternal Valsalva efforts either via Cesarean delivery under regional or general anesthesia or by choosing assisted vaginal delivery under neuraxial blockade. There is no compelling reason to offer suboccipital decompression for Chiari I malformation during pregnancy. For patients with significant neurologic symptoms prior to conception, decompression prior to pregnancy should be considered.

Spontaneous Intracranial Hemorrhage in Pregnancy: A Systematic Review of the Literature.

Stroke in pregnant women has a mortality rate of 1.4 deaths per 100,000 deliveries. Vascular malformations are the most common cause of hemorrhagic stroke in this population; preeclampsia and other risk factors have been identified. However, nearly a quarter of strokes have an undeterminable cause. Spontaneous intracranial hemorrhage (ICH) is less frequent but results in significant morbidity. The main objective of this study is to review the literature on pregnant patients who had a spontaneous ICH. A systematic review of the literature was conducted on PubMed and the Cochrane library from January 1992 to September 2016 following the PRISMA guidelines. Studies reporting pregnant patients with spontaneous intraparenchymal hemorrhage (IPH), subarachnoid hemorrhage (SAH), and subdural hemorrhage (SDH) were selected and included if patients had non-structural ICH during pregnancy or up to 6 weeks postpartum confirmed by imaging. Twenty studies were included, and 43 patients identified. Twenty-two patients (51.3%) presented with IPH, 15 patients (34.8%) with SAH, and five patients (11.6%) with SDH. The most common neurosurgical management was clinical in 76.7% of patients, and cesarean section was the most common obstetrical management in 28% of patients. The most common maternal outcome was death (48.8%), and fetal outcomes were evenly distributed among term delivery, preterm delivery, and fetal or neonatal death. Spontaneous ICH carries a high maternal mortality with IPH being the most common type, most frequently presenting in the third trimester. Diagnosis and management do not differ for the parturient compared to the non-pregnant woman.

Persistent amnion-chorion membrane separation.

AIM: Fetal membranes are composed of the amnion and chorion, which fuse during the early second trimester. Persistent separation confers increased risk of adverse perinatal outcomes. This study characterizes sonographic and placental findings associated with persistent amnion-chorion (AC) membrane separation. METHODS: This is a case series of 23 patients carrying singleton pregnancies with persistent AC membrane separation after 16 weeks' gestation diagnosed by ultrasound from 2010 to 2016 at our institution. Twenty placentas were available for analysis. RESULTS: Obstetrical complications occurred in 13 (56.5%) cases; two (8.7%) cases resulted in intrauterine fetal demise. Fetal malformations were reported in eight (34.8%) cases. Four (17.4%) neonates were small-for-gestational age (SGA; <10th percentile). Placental size measured ≤10th percentile for gestational age in eight (40%) cases. Placental cord insertion was marginal or velamentous in eight (34.8%) cases. Maternal and/or fetal placental perfusion abnormalities occurred in 11 (55%) cases. CONCLUSION: AC membrane separation is associated with adverse obstetrical outcomes, placental abnormalities, including marginal and velamentous cord insertion, placental growth restriction and placental perfusion defects. This membrane complication is associated with increased incidence of fetal malformations in the absence of identifiable genetic etiologies.

Risk of ischemic placental disease is increased following in vitro fertilization with oocyte donation: a retrospective cohort study.

PURPOSE: Assess the risk of ischemic placental disease (IPD) among in vitro fertilization (IVF; donor and autologous) pregnancies compared with non-IVF pregnancies. METHODS: This was a retrospective cohort study of deliveries from 2000 to 2015 at a tertiary hospital. The exposures, donor, and autologous IVF, were compared with non-IVF pregnancies and donor IVF pregnancies were also compared with autologous IVF pregnancies. The outcome was IPD (preeclampsia, placental abruption, small for gestational age (SGA), or intrauterine fetal demise due to placental insufficiency). We defined SGA as birthweight < 10th percentiles for gestational age and sex. A secondary analysis restricted SGA to < 3rd percentile. RESULTS: Of 69,084 deliveries in this cohort, 262 resulted from donor IVF and 3,501 from autologous IVF. Compared with non-IVF pregnancies, IPD was more common among donor IVF pregnancies (risk ratio (RR) = 2.9; 95% CI 2.5-3.4) and autologous IVF pregnancies (RR = 2.0; 95% CI 1.9-2.1), adjusted for age and parity. IVF pregnancies were more likely to be complicated by preeclampsia (donor RR = 3.8; 95% CI 2.8-5.0 and autologous RR = 2.2; 95% CI 2.0-2.5, adjusted for age, parity, and marital status), placental abruption (donor RR = 3.8; 95% CI 2.1-6.7 and autologous RR = 2.5; 95% CI 2.1-3.1, adjusted for age), and SGA (donor RR = 2.7; 95% CI 2.1-3.4 and autologous RR = 2.0; 95% CI 1.9-2.2, adjusted for age and parity). Results were similar when restricting SGA to < 3rd percentile. CONCLUSION: Pregnancies conceived using donor IVF and autologous IVF were at higher risk of IPD and its associated conditions than non-IVF pregnancies and associations were consistently stronger for donor IVF pregnancies.

Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum.

OBJECTIVE: Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. STUDY DESIGN: This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. RESULTS: TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. CONCLUSION: Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies.

Hiding in Plain Sight: Resident Remediation in Obstetrics and Gynecology.

OBJECTIVE: Residents who are in need of remediation are prevalent across residency programs and often tend to be deficient in multiple competencies that the American Council for Graduate Medical Education (ACGME) has established. The purpose of this study was to determine the prevalence of residents requiring remediation, understand the scope of the challenges in resident remediation, and assess what resources were used to aid in remediation in obstetrics and gynecology programs. DESIGN: An anonymous survey was emailed to obstetrics and gynecology program directors. Survey responses were summarized through descriptive statistics. SETTING: Obstetrics and gynecology residency program directors were invited to respond to this survey. PARTICIPANTS: Thirty-nine respondents out of 241 residency training programs responded (16%). RESULTS: The majority (84.6%) of programs had placed a resident on remediation. The most common area requiring remediation was professionalism (75.8%), followed by medical knowledge (72.7%), interpersonal communication (60.6%), laparoscopic technical skills (54.6%), and inpatient care (42.4%). Residents who required remediation were identified in a number of ways, most commonly through feedback from the Clinical Competency Committee (87.8%) and faculty feedback (84.8%). Program directors utilized a variety of resources, most commonly prior remediation plans from the program, to create remediation plans. Sixty percent of programs had residents who failed remediation. CONCLUSION: This study highlighted the prevalence of resident remediation in obstetrics and gynecology training programs and the importance of faculty in identifying residents in need of remediation, evaluating residents, and mentoring residents.

Fetal macrosomia and shoulder dystocia in women with gestational diabetes: risks amenable to treatment?

Fetal macrosomia and maternal diabetes are independent risk factors for shoulder dystocia, an obstetrical emergency that may cause permanent neonatal injury. Randomized trials of glycemic control in pregnancies complicated by gestational diabetes reveal decreased rates of macrosomia and shoulder dystocia among those treated. However, definitions of gestational diabetes vary and a specific glycemic threshold for clinically significant risk reduction remains to be delineated. This review discusses risks associated with gestational diabetes including macrosomia (birth weight above 4000-4500 g) and delivery-related morbidity, specifically, shoulder dystocia. Subsequently, we will review recent randomized trials assessing the impact of glycemic control on these delivery-related morbidities. Finally, we will examine a large observational study that found associations with delivery-related morbidity and hyperglycemia below current diabetic thresholds, observations which may suggest reexamination of current diagnosis guidelines for gestational diabetes.

Antenatal Optimization of Maternal Anemia Leads to Decreased Risks of Maternal Morbidity.

Purpose of Review: Our review focuses on the appropriate use of intravenous iron to increase the likelihood of achieving target hemoglobin levels prior to delivery to reduce maternal morbidity. Recent Findings: Iron deficiency anemia (IDA) is a leading contributor to severe maternal morbidity and mortality. Prenatal treatment of IDA has been demonstrated to reduce the likelihood of adverse maternal outcomes. Recent investigations of intravenous iron supplementation have demonstrated superior efficacy and high tolerability for the treatment of IDA in the third trimester, compared against oral regimens. However, it is unknown whether this treatment is cost-effective, available to clinicians, or acceptable to patients. Summary: Intravenous iron is superior to the oral treatment of IDA; however, its use is limited by the lack of implementation data.

Collaboration between Maternal-Fetal Medicine and Neonatology When Counseling at Extreme Prematurity.

Enhanced communication between maternal-fetal medicine (MFM)/obstetrics and neonatology regarding counseling at extreme prematurity remains an essential element of prenatal consultations. Together, the obstetrician and neonatologist can collaborate to provide timely and synergistic information to affected couples during a dynamic period, combining their expertise to elucidate values and formulate a plan that best supports the pregnant person and partner's goals. Such collaboration can help resolve differing perspectives between specialties, minimize redundancy and inconsistencies, and mitigate the impact of clinician bias. Best practices for joint-specialty collaboration include a precounseling clinician huddle, contemporaneous counseling by MFM specialists/obstetricians and neonatologists with the expectant parents or individualized sequential counseling if preferred by the couple, and a postcounseling clinician debrief. This approach can help establish a trusting relationship with families facing possible extremely preterm delivery and optimize the overall counseling experience. Future efforts focused on education and research, including a standardized approach to educational curricula among fellowship programs, should be emphasized.

A Novel Dual-Function Redox Modulator Relieves Oxidative Stress and Anti-Angiogenic Response in Placental Villus Explant Exposed to Hypoxia-Relevance for Preeclampsia Therapy.

BACKGROUND: Preeclampsia (PE) is a severe, life-threatening complication during pregnancy (~5-7%), and no causative treatment is available. Early aberrant spiral artery remodeling is associated with placental stress and the release of oxygen radicals and other reactive oxygen species (ROS) in the placenta. This precedes the production of anti-angiogenic factors, which ultimately leads to endothelial and trophoblast damage and the key features of PE. We tested whether a novel dual-function redox modulator-AKT-1005-can effectively reduce placental oxidative stress and alleviate PE symptoms in vitro. METHOD: Isolated human villous explants were exposed to hypoxia and assessed to determine whether improving cell-redox function with AKT-1005 diminished ROS production, mitochondrial stress, production of the transcription factor HIF1A, and downstream anti-angiogenic responses (i.e., sFLT1, sEng production). MitoTEMPO was used as a reference antioxidant. RESULTS: In our villous explant assays, pretreatment with AKT-1005 reduced mitochondrial-derived ROS production, reduced HIF-1A, sFLT1, and sEng protein expression, while increasing VEGF in hypoxia-exposed villous trophoblast cells, with better efficiency than MitoTEMPO. In addition, AKT-1005 improved mitochondrial electron chain enzyme activity in the stressed explant culture. CONCLUSIONS: The redox modulator AKT-1005 has the potential to intervene with oxidative stress and can be efficacious for PE therapy. Future studies are underway to assess the in vivo efficacy of HMP.

A Novel Dual-Function Nitric Oxide Donor Therapy for Preeclampsia-A Proof-of-Principle Study in a Murine Model.

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality for the mother and fetus. Reduced nitric oxide bioavailability and oxidative stress contribute to the maternal and fetal pathophysiology of PE. In this study, we evaluated the efficacy of a novel dual-function nitric oxide donor/redox modulator, AKT-1005, in reducing PE symptoms in a mouse model of PE. Method: The potential therapeutic effect of AKT-1005 was tested in an animal model of Ad.sFlt-1-induced hypertension, proteinuria and glomerular endotheliosis, a model of PE. Pregnant Ad.sFlt-1-overexpressing CD1 mice were randomized into groups administered AKT-1005 (20 mg/kg) or a vehicle using a minipump on gd11 of pregnancy, and the impact on blood pressure and renal and placental damage were assessed. Results: In healthy female mice, ex vivo treatment of resistance vessels with AKT-1005 induced vasorelaxation, and 6 days of treatment in vivo did not significantly alter blood pressure with or without pregnancy. When given for 6 days during pregnancy along with Ad.sFlt-1-induced PE, AKT-1005 significantly increased plasma nitrate levels and reduced hypertension, renal endotheliosis and plasma cystatin C. In the placenta, AKT-1005 improved placental function, with reduced oxidative stress and increased endothelial angiogenesis, as measured by CD31 staining. As such, AKT-1005 treatment attenuated the Ad.sFlt-1-induced increase in placental and free plasma soluble endoglin expression. Conclusions: These data suggest that AKT-1005 significantly attenuates the sFlt-1-induced PE phenotypes by inhibiting oxidative stress, the anti-angiogenic response, and increasing NO bioavailability. Additional research is warranted to investigate the role of AKT-1005 as a novel therapeutic agent for vascular disorders such as preeclampsia.

Timing of antibiotic administration and infectious morbidity following cesarean delivery: incorporating policy change into workflow.

PURPOSE: To evaluate the success of a multidisciplinary approach to policy change regarding timing of antibiotic administration for the prevention of surgical-site infection after cesarean delivery. METHODS: After review of the evidence, our multidisciplinary Obstetrics Leadership Committee decided to change policy on the timing of antibiotic prophylaxis for cesarean delivery. Using a combination of meetings, email communications, and local champions, 100% compliance with the new policy was achieved in 5 weeks. The effect of this policy change was investigated through a prospective cohort study of consecutive patients undergoing cesarean delivery at one institution from January 2009 through May 2009. Approximately halfway through the study period our department implemented a practice change that required antibiotic administration before skin incision rather than after clamping the umbilical cord. We compared the incidence of surgical-site infection, including endometritis, cellulitis, and total infectious morbidity, among women who received antibiotics before skin incision to those who received antibiotics after umbilical cord clamp. RESULTS: There were 533 consecutive women who underwent cesarean delivery during the study period. Two hundred forty (45.0%) women received antibiotics after cord clamping, and 285 (53.5%) women received antibiotics before skin incision; timing could not be determined for 8 (1.5%) women. Within 5 weeks of the policy change, 100% of the women undergoing cesarean delivery received perioperative prophylactic antibiotics before skin incision. The incidence of infectious morbidity fell from 5.4 to 2.5% when antibiotics were given before skin incision. Compared to the administration of antibiotics before skin incision, receiving antibiotics after cord clamp yielded a crude relative risk (RR) of 2.21 (95% CI 0.89-5.44) for total infectious morbidity and 3.56 (95% CI 0.73-17.49) for endometritis. Although not statistically significant, there was an increased risk of cellulitis (RR 1.66; 95% CI 0.53-5.17) when antibiotics were administered after cord clamping. CONCLUSIONS: A multidisciplinary approach was successful in achieving 100% adherence to our institution's policy change regarding timing of prophylactic antibiotics. This approach was necessary in order to incorporate this type of change into the labor and delivery workflow and may serve as a paradigm for success in implementing labor and delivery quality improvement projects. In addition, administration of prophylactic antibiotics before skin incision resulted in fewer surgical-site infections following cesarean delivery. As the clinical and economic impact of surgical-site infections is considerable, the once common practice of administering antibiotics after cord clamping should be avoided.

Evaluation of a rapid, real-time intrapartum group B streptococcus assay.

OBJECTIVE: We sought to evaluate an intrapartum nucleic acid amplification test (NAAT) for group B streptococcus (GBS). STUDY DESIGN: This was a prospective cohort study of 559 women comparing intrapartum GBS culture with antepartum culture and intrapartum NAAT. RESULTS: GBS prevalence was 19.5% by antepartum culture and 23.8% by intrapartum culture. Compared with intrapartum culture, antepartum culture had 69.2% sensitivity (60.6-76.9%) and 96.0% specificity (93.7-97.7%). The NAAT demonstrated sensitivity of 90.8% (84.6-95.2%), specificity of 97.6% (95.6-98.8%), and predictive values >92%. The incidence of discordant cultures was 10.4%. Of the women with negative antepartum and positive intrapartum cultures, only 1 (2.4%) received intrapartum antibiotics. Compared with white women, black (P = .02) and Hispanic (P = .02) women were more likely to have discordant cultures. CONCLUSION: This intrapartum NAAT has excellent characteristics. It may be superior to antepartum culture for detecting intrapartum GBS-allowing more accurate management of laboring mothers and reducing neonatal GBS sepsis.

Hypertensive Disorders of Pregnancy.

Preeclampsia is a hypertensive disorder of pregnancy that is a leading cause of maternal and perinatal morbidity and mortality. The condition presents heterogeneously at varying gestational ages. Primary prevention for preeclampsia with low-dose aspirin is recommended for patients with clinical risk factors. Despite extensive research, there is no clearly defined pathophysiology for preeclampsia or treatment for preeclampsia besides delivery of the placenta. Delivery of patients with preeclampsia without severe features is indicated in the early term period at 37 weeks' gestation and sooner if the patient develops severe preeclampsia. Management of preterm preeclampsia is guided by close assessment of the status of the pregnant woman and fetus, blood pressure control, and surveillance for any clinical progression to a more severe form of preeclampsia that may require preterm delivery. In a preterm gestation affected by preeclampsia, expectant management is intended to provide neonatal benefit though it does assume some maternal risk. Future research will hopefully further delineate the pathophysiology of the condition with the ultimate goal of finding a treatment to avoid associated morbidity and preterm delivery.

Angiogenic factors and prediction for ischemic placental disease in future pregnancies.

OBJECTIVES: Ischemic placental disease (IPD), including preeclampsia, abruption, and fetal growth restriction, often recurs in subsequent pregnancies. Angiogenic factors of placental origin have been implicated in the pathogenesis of preeclampsia, but have not been studied as predictors of IPD in subsequent pregnancies. We hypothesized that elevated angiogenic factors in an index pregnancy would be associated with recurrence of IPD. STUDY DESIGN: We conducted a retrospective cohort study of patients undergoing evaluation for preeclampsia who had angiogenic factors measured in an index pregnancy and experienced a subsequent pregnancy at the same institution. Patients with IPD in the index pregnancy were included. A high ratio of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) was defined as greater than or equal to 85. MAIN OUTCOME MEASURES: The primary outcome was IPD in a subsequent pregnancy. RESULTS: We included 109 patients in the analysis. The sFlt1/PlGF ratio was elevated in 30% of participants. Those with an elevated ratio were more likely to be nulliparous in the index pregnancy, and less likely to have chronic hypertension. The recurrence of IPD in the study was 27%, with a non-significant difference in risk based on a high sFlt-1/P1GF ratio RR 0.58 (95% CI 0.21 - 1.6) compared to a low ratio. CONCLUSIONS: A high sFlt1/P1GF ratio in an index pregnancy is not associated with a higher risk of IPD in a subsequent pregnancy. These data suggest placental angiogenic biomarkers are specific to the pregnancy and not a reflection of maternal predisposition to IPD.

Association between in vitro fertilization and ischemic placental disease by gestational age.

OBJECTIVE: To evaluate the association between in vitro fertilization (IVF) and ischemic placental disease (IPD), stratified by gestational age. DESIGN: We performed a secondary analysis of a retrospective cohort study of deliveries. SETTING: Deliveries were performed over 15 years at a single tertiary hospital. PATIENT(S): We included all parturients who had a live born infant or an intrauterine fetal demise (IUFD). INTERVENTION(S): We compared pregnancies resulting from IVF cycles to non-IVF pregnancies. MAIN OUTCOME MEASURE(S): The primary outcomes were preterm and term IPD (preeclampsia, placental abruption, small-for-gestational age infant [SGA], or an intrauterine fetal demise [IUFD] due to placental insufficiency). RESULT(S): Of the 69,084 deliveries during the study period, 3,763 (5.4%) were conceived with IVF. The incidence of preterm delivery was 32.6% in IVF pregnancies and 10.8% in non-IVF pregnancies. Multiple gestations were more common in IVF pregnancies. Compared to non-IVF pregnancies, IVF pregnancies were more likely to develop both preterm and term IPD, even after adjustment for maternal age and parity. The risk of preterm IPD was 4 times higher (95% confidence interval, 3.7-4.4) in patients who underwent IVF compared with those who did not undergo IVF. Among parturients who delivered at ≥37 weeks of gestation, IVF pregnancies had 1.7 times the risk of term IPD (95% confidence interval, 1.6-1.9) compared with non-IVF pregnancies. CONCLUSION(S): IVF was strongly associated with preterm IPD. We found a similar, but attenuated, association between IVF and term IPD. The stronger association with preterm IPD suggests an association between IVF and placental insufficiency.