Management Of Subsequent Pregnancies Research Articles

SARS-CoV-2-Placental effects and association with stillbirth.

SARS-CoV-2 has had a significant impact on pregnancy outcomes due to the effects of the virus and the altered healthcare environment. Stillbirth has been relatively hidden during the COVID-19 pandemic, but a clear link between SARS-CoV-2 and poor fetal outcome emerged in the Alpha and Delta waves. A small minority of women/birthing people who contracted COVID-19 developed SARS-CoV-2 placentitis. In many reported cases this was linked to intrauterine fetal death, although there are cases of delivery just before imminent fetal demise and we shall discuss how some cases are sub-clinical. What is surprising, is that SARS-CoV-2 placentitis is often not associated with severe maternal COVID-19 infection and this makes it difficult to predict. The worst outcomes seem to be with diffuse placental disease which occurs within 21 days of COVID-19 diagnosis. Poor outcomes are often pre-dated by reduced fetal movements but are not associated with ultrasound changes. In some cases, there has also been maternal thrombocytopenia, or coagulation abnormalities, which may provide a clue as to which pregnancies are at risk of fetal demise if a further variant of concern is to emerge. In future, multidisciplinary collaboration and cross-boundary working must be prioritised, to identify quickly such a phenomenon and provide clinicians with clear guidance for reducing fetal death and associated poor outcomes. While we wait to see if COVID-19 brings a future variant of concern, we must focus on appropriate future management of women who have had SARS-CoV-2 placentitis. As a placental condition with an infectious aetiology, SARS-CoV-placentitis is unlikely to recur in a subsequent pregnancy and thus a measured approach to subsequent pregnancy management is needed.

The challenging follow-up of pregnancy in women with known thrombotic thrombocytopenic purpura: a single-center experience of a preemptive management protocol.

Although thrombotic thrombocytopenic purpura frequently affects women of childbearing age, there is no clear recommendation for the management of subsequent pregnancies in women with established thrombotic thrombocytopenic purpura. This single-center, retrospective, observational study included all women with hereditary thrombotic thrombocytopenic purpura or immune thrombotic thrombocytopenic purpura who had had at least one subsequent pregnancy after thrombotic thrombocytopenic purpura diagnosis between 2003 and 2022. The strategy comprised weekly surveillance of platelet count during pregnancy (and quarterly monitoring of ADAMTS13 activity) for women with immune thrombotic thrombocytopenic purpura, without any routine prophylactic treatment. In case of thrombocytopenia < 150,000/mm3 (with or without hemolysis relapse), women with hereditary thrombotic thrombocytopenic purpura systematically received plasma infusions twice weekly until platelet count normalized. A total of 13 patients were included (7 with hereditary thrombotic thrombocytopenic purpura and 6 with immune thrombotic thrombocytopenic purpura, with 20 planned pregnancies (11 and 9, respectively). All pregnancies resulted in live births, and all mothers survived.There was a marked improvement in pregnancy terms in the hereditary thrombotic thrombocytopenic purpura group compared to index pregnancies (37 [35;39] versus 31 [24;38] weeks, p = 0.037) and birth weights (3265 [3029;3410] versus 2160 [1240;2705] grams, p = 0.016), with need for plasma support mostly starting during the third trimester (5/7 patients, 7/11 pregnancies). A single hereditary thrombotic thrombocytopenic purpura relapse occurred, with rapid resolution after plasma support intensification. There were no relapses in the immune thrombotic thrombocytopenic purpura group, with ADAMTS13 activity systematically above 40% during all monitored pregnancies. These real-life data support the feasibility of a preemptive approach to pregnancy monitoring in women with known thrombotic thrombocytopenic purpura who undergo active surveillance within a multidisciplinary network.

Whole-exome sequencing in deceased fetuses with ultrasound anomalies: a retrospective analysis

BackgroundWhole-exome sequencing (WES) is an effective method in the prenatal setting for identification of the underlying genetic etiology of fetal ultrasound abnormalities. To investigate the diagnostic value of WES in fetuses with ultrasound abnormalities that resulted in fetal demise or pregnancy termination.Methods61 deceased fetuses with ultrasound abnormalities and normal copy number variation Sequencing were retrospectively collected. Proband-only or trio-WES were performed on the products of conception.ResultCollectively, 28 cases were positive with 39 variants (10 pathogenic, 22 likely pathogenic and 7 variants of uncertain significance) of 18 genes, and the overall diagnostic rate was 45.9% (28/61), of which 39.2% (11/28) were de novo variants. In addition, 21 variants in 11 genes among the positive cases had not been previously reported. The diagnostic yield for definitive findings for trio analysis was 55.9% (19/34) compared to 33.3% (9/27) for singletons. The most common ultrasound abnormalities were skeletal system abnormalities 39.2% (11/28), followed by multiple system abnormalities (17.9%, 5/28) and genitourinary abnormalities (17.9%, 5/28).ConclusionOur results support the use of WES to identify genetic etiologies of ultrasound abnormalities and improve understanding of pathogenic variants. The identification of disease-related variants provided information for subsequent genetic counseling of recurrence risk and management of subsequent pregnancies.

The uncertainty of copy number variants: pregnancy decisions and clinical follow-up

Next-generation sequencing for copy number variants is often used as a follow-up investigation of unusual fetal ultrasound results and is capable of detecting copy number variations with a resolution of ∼0.1 Mb. In a prenatal setting, observation and subsequent management of pregnancies with a fetal variant of uncertain significance remains problematic for counseling. This study aimed to follow the decision-making processes in pregnancies with a fetal variant of uncertain significance and prospectively assess copy number variation interpretations and implications under the newer 2020 American College of Medical Genetics and Genomics guidelines. In a single prenatal unit, prospective chromosome testing using copy number variation sequencing for 8030 fetuses with unexpected noninvasive findings identified 139 pregnancies with a copy number variation classified as a variant of uncertain significance according to the 2015 American College of Medical Genetics and Genomics guidelines current at the time. Parent-of-origin testing was subsequently performed to determine if the copy number variation was inherited or de novo. All couples were offered specialized genetic counseling to assist in pregnancy management decisions. For the continued pregnancies that reached term, newborns were clinically assessed for evidence of any disease at 0 to 10 months and/or at 2 to 4 years of age. Of the 139 variants of uncertain significance found, most (78%) were inherited with no evidence of disease in the carrier parent. On the basis of primary ultrasound findings combined with results from noninvasive prenatal screening tests, most inherited variant of uncertain significance pregnancies were continued, whereas most pregnancies involving de novo variants of uncertain significance were terminated. From clinical follow-up of the 113 live births, only 5 showed any evidence of a phenotype that was not apparently related to the original variant of uncertain significance. Prospective reanalysis of the 139 variants of uncertain significance using recent 2020 American College of Medical Genetics and Genomics guidelines changed the status of 24 variants of uncertain significance, with 15 reclassified as benign and 9 as pathogenic. However, the 5 children born with an inherited variant of uncertain significance reclassified as pathogenic showed no evidence of a disease phenotype on clinical follow-up. The severity of fetal ultrasound findings combined with results from parent-of-origin testing were the key drivers in pregnancy management decisions for patients. According to birth outcomes from continued pregnancies, most variants of uncertain significance proved to be apparently benign in nature and potentially of low risk of adverse disease outcome. There was a discordance rate of 17% for variant of uncertain significance scoring between the 2015 and 2020 American College of Medical Genetics and Genomics guidelines for defining a variant of uncertain significance, suggesting that difficulties remain for predicting true pathogenicity. Nonetheless, with increasing knowledge of population copy number variation polymorphisms, and a more complete assessment for alternative genetic causes, patients having prenatal assessments should feel less anxious when a fetal variant of uncertain significance is identified.

Critical analysis of risk factors for intrapartum death

Intrapartum fetal death is devastating for both parents and medical caregivers. Management in subsequent pregnancies is often based on risk factors. The purpose of this study was to evaluate risk factors for intrapartum fetal death.

Clinical presentation, investigation, underlying causes, and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage.

To evaluate the causes of miscarriage and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage. Retrospective analysis of 170 consecutive second trimester miscarriages between 14 + 0 and 23 + 6 weeks recorded in the Clinical Data Analysis and Reporting System from 2012 to 2021. Cases were excluded if miscarriages occurred before 14 + 0 weeks of gestation, data were incomplete, or passage of the fetus happened before the clinical assessment. Cases were classified with a stepwise approach into three phenotypic groups including silent miscarriages (ST-SM), rupture of membranes (ST-ROM), and inevitable miscarriages (ST-IM) depending on the fetal heart pulsation and leakage of liquor at presentation. Clinical investigation of the underlying causes and the outcome of the subsequent pregnancy was then reviewed. There were 97 cases of ST-SM, 21 cases of ST-ROM, and 52 cases of ST-IM. Placental histology and karyotype examination were more likely to yield significant results in the cases of ST-ROM and ST-SM (p < 0.05). The phenotypic examination identified different underlying causes including fetal anomaly, suspected cervical insufficiency, diabetes mellitus, and unknown causes (p < 0.001). Sixty-four cases achieved a subsequent pregnancy. Although women with history of ST-ROM and ST-IM received more cervical length monitoring and cervical cerclage than those with ST-SM (66.7% vs. 44.4% vs. 7.5%, p=0.0002; and 16.7% vs. 22.2% vs. 2.5%, p=0.031, respectively), the risk of recurrent second trimester miscarriage was higher in ST-ROM and ST-IM than in ST-SM (16.7% vs. 0%, p=0.018). The classification can differentiate different second trimester miscarriage phenotypes, which offers essential information to guide investigation panels of the underlying cause of miscarriages, and the prognosis and management of subsequent pregnancy. Future researches focused on second trimester miscarriage should report their findings according to different phenotypes.

Critical analysis of risk factors for intrapartum fetal death.

Intrapartum fetal death is devastating for both parents and medical caregivers. The purpose of this study was to evaluate the risk factors for intrapartum fetal death, which often influence management in subsequent pregnancies. This population-based cohort study included all singleton deliveries between the years 1991-2016 at Soroka University Medical Center. Trends over the years, risk factors for intrapartum fetal death and the effect of day of the week were examined. A generalized estimation equation (GEE) model was used to control for confounders. During the study period 344,536 deliveries were recorded, of which 251 (0.1%) suffered intrapartum fetal death. Rates did not change significantly over the years (p = 0.130, using the chi-square test for trends). Preterm delivery, placental abruption, uterine rupture, shoulder dystocia, congenital malformations, severe preeclampsia and fetal malpresentation were significantly more common in pregnancies complicated by intrapartum death. Using a GEE model; shoulder dystocia (aOR 23.8, 95% CI 9.9-57.3, p < 0.005), uterine rupture (aOR 19.0, 95% CI 7.0-51.4, p < 0.05), preterm delivery (aOR 11.9, 95% CI 8.6-16.5, p < 0.001), placental abruption (aOR 6.2, 95% CI 4.1-9.4, p < 0.001), fetal malpresentation (aOR 3.6, 95% CI 2.6-4.9, p < 0.005) and congenital malformations (aOR 2.6, 95% CI 1.9-3.5, p < 0.05) were all independent risk factors for intrapartum fetal death. Weekend deliveries were not at increased risk of intrapartum fetal death. Several risk factors were identified for intrapartum fetal death, with shoulder dystocia demonstrating the highest risk. Unfortunately most factors are neither preventable nor predictable and interventions to decrease the rate of intrapartum fetal death remain elusive.

Universal Urogynecologic Consultation and Screening for Fecal Incontinence in Pregnant Women With a History of Obstetric Anal Sphincter Injury: A Cost-Effectiveness Analysis.

Obstetric anal sphincter injuries (OASIS) predispose for the development of fecal incontinence (FI), but management of subsequent pregnancy after OASIS is controversial. We aimed to determine if universal urogynecologic consultation (UUC) for pregnant women with prior OASIS is cost-effective. We performed a cost-effectiveness analysis of pregnant women with a history of OASIS modeling UUC compared with no referral (usual care). We modeled the route of delivery, peripartum complications, and subsequent treatment options for FI. Probabilities and utilities were obtained from published literature. Costs using a third-party payer perspective were gathered from the Medicare physician fee schedule reimbursement data or published literature converted to 2019 U.S. dollars. Cost-effectiveness was determined using incremental cost-effectiveness ratios). Our model demonstrated that UUC for pregnant patients with prior OASIS was cost-effective. Compared with usual care, the incremental cost-effectiveness ratio for this strategy was $19,858.32 per quality-adjusted life-year, below the willingness to pay a threshold of $50,000/quality-adjusted life-year. Universal urogynecologic consultation reduced the ultimate rate of FI from 25.33% to 22.67% and reduced patients living with untreated FI from 17.36% to 1.49%. Universal urogynecologic consultation increased the use of physical therapy by 14.14%, whereas rates of sacral neuromodulation and sphincteroplasty increased by only 2.48% and 0.58%, respectively. Universal urogynecologic consultation reduced the rate of vaginal delivery from 97.26% to 72.42%, which in turn led to a 1.15% increase in peripartum maternal complications. Universal urogynecologic consultation in women with a history of OASIS is a cost-effective strategy that decreases the overall incidence of FI, increases treatment utilization for FI, and only marginally increases the risk of maternal morbidity.

Investigation and management of stillbirth: a descriptive review of major guidelines.

Stillbirth is a common and devastating pregnancy complication. The aim of this study was to review and compare the recommendations of the most recently published guidelines on the investigation and management of this adverse outcome. A descriptive review of guidelines from the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynecologists (RCOG), the Perinatal Society of Australia and New Zealand (PSANZ), the Society of Obstetricians and Gynecologists of Canada (SOGC) on stillbirth was carried out. Regarding investigation, there is consensus that medical history and postmortem examination are crucial and that determining the etiology may improve care in a subsequent pregnancy. All guidelines recommend histopathological examination of the placenta, genetic analysis and microbiology of fetal and placental tissues, offering less invasive techniques when autopsy is declined and a Kleihauer test to detect large feto-maternal hemorrhage, whereas they discourage routine screening for inherited thrombophilias. RCOG and SOGC also recommend a complete blood count, coagulopathies' testing, anti-Ro and anti-La antibodies' measurement in cases of hydrops and parental karyotyping. Discrepancies exist among the reviewed guidelines on the definition of stillbirth and the usefulness of thyroid function tests and maternal viral screening. Moreover, only ACOG and RCOG discuss the management of stillbirth. They agree that, in the absence of coagulopathies, expectant management should be considered and encourage vaginal birth, but they suggest different labor induction protocols and different management in subsequent pregnancies. It is important to develop consistent international practice protocols, in order to allow effective determination of the underlying causes and optimal management of stillbirths, while identifying the gaps in the current literature may highlight the need for future research.

A STUDY OF THE MORPHOLOGY OF PLACENTA IN TERTIARY CARE HOSPITAL OF CENTRAL KARNATAKA, INDIA

Introduction: Placenta is a temporary structure, developed during Pregnancy and discarded at Parturition. Human Placenta is of Discoid and Haemo-Chorial type. It connects the foetus with the mother's womb. It is formed by the contribution of two Individuals - both Mother and Baby. At 1 term four- fth of Placenta is of foetal origin and one- fth is of maternal. Along with Amnion, Chorion, Allantois and Yolk sac, Placenta can also be considered as one of the foetal membranes, which acts as Nutritive and Protective to the developing Embryo. Method: - The present study was done on morphology and morphometry of 150 placentae carried at the Department of Anatomy, Basaveshwara Medical College &amp; Hospital (BMCH), Chitradurga. The placentae were collected with prior ethical clearance and proper consent. Soon after the delivery the placental surface was washed thoroughly under running tap water which were then weighed, tagged and brought to the department of Anatomy, BMCH. The parameters like size, shape and attachment of umbilical cord were noted down. Gross examination was carried out according to the proforma. Result: - The maximum number of placentae belong to the range of 501-600 gms (38.7%). Least placental weight is recorded as 205 gms, showing dispersal pattern. The maximum recorded weight is 835 gms and the average being 491.4 gms. The majority of the placentae are discoid (63.3%). The minimum length recorded is 8.9 cms, maximum as 23.80 cms and the average being 18.3 cms. Conclusion: - Careful examination of Placenta can help in explaining adverse outcomes, their management in subsequent pregnancies and assessment of new born risk.

47 Universal screening for fecal incontinence in pregnant women with a history of obstetric anal sphincter injury: A cost-effectiveness analysis

Fecal incontinence (FI), the involuntary passage of solid or liquid stool or mucus from the rectum, can have devastating effects on quality of life and presents a significant healthcare cost burden. Obstetric anal sphincter injuries (OASIS) are a known risk factor for the development of FI, but management of subsequent pregnancy after OASIS is controversial. The objective of this study is to determine if universal urogynecologic screening for FI for pregnant women with prior OASIS is cost-effective. We performed a cost-effectiveness analysis using a decision tree model. For pregnant women with history of OASIS in a previous delivery, we modeled the option of referral to urogynecology (FI screening) compared to no referral (usual care). From there, we modeled the option of proceeding with an elective cesarean delivery or trial of labor as well as the actual delivery method (vaginal, planned cesarean, or unplanned cesarean). A second sub-tree was constructed with branch points modeling the probabilities of various maternal peripartum complications. A third sub-tree modeled the treatment options for patients who developed FI. Probabilities used in the model were obtained from the published literature using PubMed to find relevant primary sources. Utilities used in the model were obtained from the Tufts Medical Center Cost-Effectiveness Analysis Registry if available. Otherwise, they were obtained from the published literature. We used the cost perspective of a third-party payer. Costs were gathered from the Medicare physician fee schedule reimbursement data or published literature and were converted to 2019 US dollars via consumer price index tables and year-specific currency conversion rates to account for inflation. Our primary outcome of cost-effectiveness was determined by using the incremental cost-effectiveness ratio (ICER). Model robustness was assessed using multiple 1-way sensitivity analyses. Our model demonstrated that universal FI screening and referral to urogynecology for pregnant patients with prior OASIS was cost-effective. Compared to the usual care strategy of no screening, the ICER for this strategy was $19,858.32/QALY, well below the WTP threshold of $50,000/QALY. Screening for FI reduced the ultimate rate of FI by 2.65% and reduced the ultimate rate of patients living with untreated FI by 15.87%. Screening increased the use of pelvic floor PT by 14.14% while rates of second and third-line surgical FI treatments (sacral neuromodulation or sphincteroplasty) increased by only 2.48% and 0.58%, respectively. The screening strategy reduced the rate of vaginal delivery by 24.84%, which in turn led to a 1.15% increase in the rate of peripartum maternal complications. Universal screening for fecal incontinence in women with a prior history of OASIS is a cost-effective strategy that decreases the overall incidence of FI, increases the utilization of treatment for FI, and only marginally increases the risk of maternal morbidity.

Exome sequencing analysis on products of conception: a cohort study to evaluate clinical utility and genetic etiology for pregnancy loss

Pregnancy loss ranging from spontaneous abortion (SAB) to stillbirth can result from monogenic causes of Mendelian inheritance. This study evaluated the clinical application of exome sequencing (ES) in identifying the genetic etiology for pregnancy loss. A cohort of 102 specimens from products of conception (POC) with normal karyotype and absence of pathogenic copy-number variants were selected for ES. Abnormality detection rate (ADR) and variants of diagnostic value correlated with SAB and stillbirth were evaluated. ES detected 6 pathogenic variants, 16 likely pathogenic variants, and 17 variants of uncertain significance favor pathogenic (VUSfp) from this cohort. The ADR for pathogenic and likely pathogenic variants was 22% and reached 35% with the inclusion of VUSfp. The ADRs of SAB and stillbirth were 36% and 33%, respectively. Affected genes included those associated with multisystem abnormalities, neurodevelopmental disorders, cardiac anomalies, skeletal dysplasia, metabolic disorders, and renal diseases. These results supported the clinical utility of ES for detecting monogenic etiology of pregnancy loss. The identification of disease-associated variants provided information for follow-up genetic counseling of recurrence risk and management of subsequent pregnancies. Discovery of novel variants could provide insight for underlying molecular mechanisms causing fetal death.

964 Prior spontaneous preterm birth: subsequent pregnancy outcomes among women with PPROM vs spontaneous preterm labor

Women with a history of spontaneous preterm birth (sPTB) are at an increased risk for recurrent preterm birth. Preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) have potentially varying mechanisms and etiopathogenesis. The objective of our study was to evaluate the differential impact of history of PPROM vs sPTL on subsequent pregnancy management and perinatal outcomes. Retrospective review of women delivering at a single hospital from July 2018- November 2019 to identify women with a history of sPTB of singleton gestations. The cohort was divided into two groups based on a history of sPTL vs PPROM. Demographic data, pregnancy management, and perinatal outcomes were abstracted through a review of electronic medical records and compared across the 2 groups using student’s t test and chi squared/Fischer’s exact test for continuous and categorical data respectively. Out of 2,803 women, 168 women had a history of sPTB: 125 (74%) with a history of sPTL and 43 (23%) with a history of PPROM. Demographic characteristics were similar across groups. We found no significant differences in the pregnancy interventions (Table 1) and perinatal outcomes (Table 2) among study groups. Subgroup analyses were performed evaluating the impact of vaginal vs IM progesterone. While there were no significant differences noted in women with a history of PPROM, differences were noted among women with a history of sPTL. Women who received IM progesterone had longer cervical lengths (mean ± SD) [36.3mm ± 4.4; N=21 vs 20.5 ± 12.2; N=18 p<0.001] and delivered at a later gestational age (mean ± SD) (37.2 ± 1.6 weeks; N=28 vs 34.7 ± 5.6 weeks; N = 23) as compared to women receiving vaginal progesterone. In our cohort, similar outcomes were noted in subsequent pregnancies among women with history of PPROM and sPTL. However, subgroup analyses in women with a history of sPTL suggest a potential benefit of IM progesterone. Further research in a larger cohort is warranted to delineate the differential impact of the history of sPTB in the context of PPROM vs sPTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Uterine Dehiscence and Subsequent Pregnancy Management: A Review of the Literature.

Uterine dehiscence is a separation of the uterine musculature with intact uterine serosa. Uterine dehiscence can be encountered at the time of cesarean delivery, be suspected on obstetric ultrasound, or be diagnosed in between pregnancies. Management is a conundrum for obstetricians, regardless of timing of onset. A literature search was undertaken by our research librarian using the search engines PubMed, CINAHL, and Web of Science. The search term used was "uterine dehiscence." The search was limited to the English language, and there was no limit on the years searched. The search identified 152 articles, 32 of which are the basis for this review. Risk factors, treatment, and management in subsequent pregnancies are discussed. The number of prior cesarean deliveries is the greatest risk factor for uterine dehiscence. Unrepaired uterine dehiscence can cause symptoms outside of pregnancies and may require repair for alleviation of these symptoms. Dehiscence should also be repaired prior to subsequent pregnancies. Planned delivery prior to the onset of labor with careful monitoring of maternal symptoms is the preferred management strategy of women with prior uterine dehiscence. Careful attention should be paid to the lower uterine segment thickness when ultrasonography is performed in women with prior cesarean delivery. An evidence-based review of uterine dehiscence in pregnancy and how to manage subsequent pregnancies following uterine dehiscence.

Fetal and Neonatal Alloimmune Thrombocytopenia-New Prospects for Fetal Risk Assessment of HPA-1a-Negative Pregnant Women.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially serious bleeding condition in the fetus/newborn. FNAIT is usually considered as the platelet counterpart of hemolytic disease of the fetus and newborn. In FNAIT, maternal alloantibodies against paternally inherited platelet antigens traverse the placenta and cause thrombocytopenia in the fetus/newborn. The most common and most serious cases of FNAIT among white people are caused by alloantibodies against the human platelet antigen 1a (HPA-1a), which is absent in 2.3% of women. Today, there is no screening for FNAIT, and for this reason, FNAIT is not suspected until an otherwise healthy child, born at term, presents with thrombocytopenia. Clinical management of subsequent pregnancies at risk of FNAIT is mostly based on the obstetric history. During the last 5 decades, hemolytic disease of the fetus and newborn caused by antibodies against RhD has successfully been prevented by administration of hyperimmune anti-D IgG drug products to RhD-negative women after delivery of an RhD-positive child. Similarly, a hyperimmune anti-HPA-1a IgG (NAITgam) is under development for the prevention of HPA-1a immunization and FNAIT. If NAITgam becomes licensed for FNAIT prophylaxis and national health authorities decide to include FNAIT screening in their antenatal health care programs, it will be necessary to improve today's tools for assessing the risk of FNAIT. Although the primary risk factor for HPA-1a immunization is platelet type HPA-1bb, not all HPA-1a-negative women develop anti-HPA-1a. The women who are HLA-DRB3:01:01 negative (72%) only rarely develop anti-HPA-1a, and for those few who become HPA-1a immunized, it is quite rare to have a child with severe thrombocytopenia. Determination of fetal HPA-1 type is important because 15% of HPA-1a-negative women will carry an HPA-1a-negative fetus and therefore not be at risk of FNAIT. The severity of FNAIT seems to be associated with the level of anti-HPA-1a. Hence, in Norway, for example, an Ab threshold of 3 IU/mL is used to distinguish between low- and high-risk pregnancies. The current review will discuss to what extent these analyses, as well as determination of subtypes of anti-HPA-1a (anti-β3, anti-αIIbβ3, and anti-αvβ3) and Fc core fucosylation of anti-HPA-1a IgG, can be used as risk stratification tools.

The Childbirth Experience Questionnaire (CEQ)-Validation of its use in a Danish-speaking population of new mothers stimulated with oxytocin during labour.

BackgroundWhen determining optimal treatment regimens, patient reported outcomes including satisfaction are increasingly appreciated. It is well established that the birth experience may affect the postnatal attachment to the newborn and the management of subsequent pregnancies and deliveries. As we have no robust validated Danish tool to evaluate the childbirth experience exists, we aimed to perform a transcultural adaptation of the Childbirth Experience Questionnaire (CEQ) to a Danish context.MethodsIn accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN), we translated the Swedish-CEQ to Danish. The Danish-CEQ was tested for content validity among 10 new mothers. In a population of women who have had their labour induced, we then assessed the electronic questionnaire for validity and reliability using factor analytical design, hypothesis testing, and internal consistency. Based on these data, we determined criterion and construct responsiveness in addition to floor and ceiling effects.ResultsThe content validation resulted in minor adjustments in two items. This improved the comprehensibility. The electronic questionnaire was completed by 377 of 495 women (76.2%). The original Swedish-CEQ was four-dimensional, however an exploratory factor analysis revealed a three-dimensional structure in our Danish population (Own capacity, Participation, and Professional support). Parous women, women who delivered vaginally, and women with a labour duration <12 hours had a higher score in each domain. The internal consistency (Cronbach’s alpha) ranged between 0.75 and 0.89 and the ICC between 0.68–0.93. We found ceiling effects of 57.6% in the domain Professional support and of 25.5% in the domain Participation.ConclusionThis study offers transcultural adaptation of the Swedish-CEQ to a Danish context. The 3-dimensional Danish-CEQ demonstrates construct validity and reliability. Our results revealed significant ceiling effect especially in the domain Professional support, which needs to be acknowledged when considering implementing the Danish-CEQ into trials and clinical practice.

Management of subsequent pregnancies following fourth-degree obstetric anal sphincter injuries (OASIS)

ObjectivesThe management of subsequent pregnancy in women who sustained OASIS remains an enigma. Nearly all studies include all grades of OASIS including fourth-degree tears. In addition, most protocols require endoanal ultrasound and anal manometric assessment to provide advice regarding mode of delivery. In reality, most women who sustain an OASI do not undergo these investigations. The aims of our study were firstly to evaluate outcomes of fourth-degree OASIS in terms of sphincter defects, anal manometry and anal incontinence symptoms. Secondly, we wished to review recommendations made regarding subsequent mode of delivery after fourth-degree OASIS according to different published protocols. Study designAn observational study of all women who had undergone a primary repair of a fourth-degree tear and seen in the perineal clinic of a tertiary urogynaecology unit between January 2006 and December 2017. Three-dimensional endoanal ultrasound and anal manometry were performed on all women, and symptoms assessed using the validated modified St Mark’s Score for anal incontinence. Diagnostic test accuracy analysis was performed for use of symptoms in predicting abnormal investigations. Results74 fourth-degree tears were identified (mean follow-up 5.9 months; SD 11.5). Endoanal scan showed an internal anal sphincter defect in 77 % and an external anal sphincter defect in 49 %. Only 18 % had no defect. The mean incremental pressure rise was 12.6 mmHg (SD 15.5). 61 % were asymptomatic with a mean St Mark’s Score of 3.8 (SD 5.4). The presence of symptoms alone had poor accuracy in predicting abnormal investigations. Based on Royal College of Obstetricians and Gynaecologists guidance, only 7% would not be offered a caesarean section as they are asymptomatic women with normal scan and manometry findings and would be counselled for a vaginal delivery. ConclusionsGiven that only a few units offer these specialist investigations to their OASI population, it would be reasonable to offer caesarean section to all women who have sustained a fourth-degree tear. However, in centres where endoanal ultrasound and anal manometry are available, individualised counselling can be offered.

161: Risk factors for Recurrent Stillbirth (SB): Results from the Stillbirth Collaborative Research Network (SCRN)

Prior stillbirth (SB) is one of the strongest independent risk factor for subsequent SB. We sought to identify risk factors for recurrent SB in women who have experienced previous SB in hopes of identifying key risk factors to assist in guiding management of subsequent pregnancies. SCRN was a population-based case control study of women with SB and contemporary enrollment of women with live births (LB). Stillbirth was defined as Apgars 0 and 0 at 1 and 5 minutes in pregnancies ≥18 weeks gestation. Of women enrolled in SCRN, we identified 93 who had experienced a previous SB at time of enrollment. Of this cohort, 50 patients with a prior SB had pregnancies ending in LB (out of n=1394); while 43 experienced a subsequent SB (out of n=470). Medical and delivery outcome data for their pregnancies were abstracted from the medical record. Chi-square testing was performed to determine correlation between subsequent SB, maternal demographic data, and obstetrical complications. A logistic regression analysis was performed to assess the gestational age trends at which patients were most at risk for consecutive stillbirth. None of the risk factors or obstetric co-morbidities analyzed were associated with an increased risk for subsequent SB (Table 1). While there was a trend toward greater risk for subsequent SB in women of African descent (p=0.097) and with lower paternal education levels (p=0.07), these trends did not reach significance and are not modifiable. Subsequent stillbirth was more commonly encountered at earlier gestational ages than in the third trimester or at term, although a substantial proportion occurred after 32 weeks gestation (Figure 1). While it is known that women who have had previous stillbirths are at increased risk of subsequent stillbirths, we identified no specific modifiable risk factors for recurrent stillbirth in our cohort. Almost 20% of the recurrent SB occurred after 37 weeks, reflecting an opportunity for improvement.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Managing the Unusual Causes of Fetal Anemia

Background: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists. Objectives: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies. Method: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d’Hémobiologie Périnatale) and born between 2010 and 2017. Results: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21–33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18–0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death. Conclusions: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.

Successful Vaginal Delivery in a Woman with Previous Caesarean Scar Ectopic Pregnancy: A Case Report and Literature Review

Background: Caesarean scar implantation is a rare form of ectopic pregnancy. Subsequent pregnancies following CSP is usually associated with complications such as first or second trimester miscarriage, placenta previa or accreta causing life threatening haemorrhage, emergency hysterectomy and uterine rupture threatening lives of mother and fetus. Given the lack of consensus on treatment modalities of CSP and subsequent pregnancy, babies are usually delivered by caesarean section at term. We report on a case describing uncomplicated pregnancy course and successful vaginal delivery of a woman who had had caesarean scar ectopic pregnancy previously. Case: We report on a case of 38 year old, Gravida 7 P2+4, who was diagnosed with a CSP in her 5th pregnancy and was managed by evacuation of caesarean scar ectopic pregnancy. She presented to us again on her 7th pregnancy in early pregnancy assessment unit (EPAU) at 7+6 weeks. As she had recurrent miscarriage, Aspirin, Tinzaparin and Cyclogest were started after dating scan. She also developed gestational diabetes, hence, Metformin and Insulin was initiated. She was induced with Dinoprostone at 37+3weeks of pregnancy. Labour was conducted under epidural analgesia and the fetus was continuously monitored throughout labour. Obstetric management was largely based upon current literature and professional experience as there are not sufficient relevant cases published in literature neither specific guideline for the management in subsequent pregnancy after CSP. Results: A Healthy baby of birth weight 3.19kg was delivered without complications with second degree perineal tear. Conclusion: Although, subsequent pregnancy following caesarean scar pregnancy is associated with significant morbidity at all stages of pregnancy, hence, is recommended to deliver women by caesarean section at term, this case demonstrates that vaginal delivery is an option with careful case selection, close monitoring and informed consent from patient