Characteristics of Pregnancy Course in an Infant With Cerebral Palsy Showing Decreased Fetal Movement

To describe how decreased fetal movement (DFM) was managed in patients with fetomaternal hemorrhage (FMH) and to evaluate the diagnostic limitations of this condition in real-world settings. This retrospective cohort study included individuals who developed FMH with cerebral palsy from the Japanese nationwide cerebral palsy registry between 2009 and 2022. We investigated whether patients experienced DFM or were prenatally diagnosed with FMH. Furthermore, we assessed how DFM was managed. This study included 57 patients who developed FMH with cerebral palsy, and none were prenatally diagnosed with FMH. DFM was present in 43/57 (75.4%) patients. A sinusoidal pattern was observed in 29/57 (50.9%) patients, and elevated middle cerebral artery peak systolic velocity (MCA-PSV) was detected in 6/10 (60.0%) patients who underwent this test. Of the 43 patients with DFM, 42 (97.7%) sought medical care for this symptom; however, only 12 (27.9%) underwent examinations on the same day as the onset of DFM, and 9 (20.9%) were admitted on that same day. Furthermore, 6/43 (14.0%) were instructed to stay home after telephone consultation or medical examination for this symptom. In five of the 43 patients (11.6%) who experienced DFM, the initial non-stress test was reactive. However, all these patients eventually developed either a non-reactive or non-reassuring fetal status. DFM was prevalent among pregnancies complicated by FMH; however, it was often inadequately managed, resulting in diagnostic delays. Furthermore, fetal heart rate monitoring and MCA-PSV evaluations had diagnostic limitations. To facilitate early treatment, clinicians need to promptly assess preceding DFM while recognizing the limitations of existing tests.

To investigate the association between abnormal cord insertion and the development of twin-specific complications, including birth-weight discordance, selective fetal growth restriction (sFGR) and twin-to-twin transfusion syndrome (TTTS). This was a single center retrospective cohort study of twin pregnancies. Abnormal cord insertion was defined as either marginal (umbilical cord attachment site less than 2 cm to the nearest margin of the placental disc) or velamentous (cord attached to the membrane before reaching the placental disc with clear evidence of vessels traversing the membranes to connect with the placental disc), as described in placental pathology reports. Twins with major structural or chromosomal abnormalities and monochorionic monoamniotic twins were not included in the study. Information on the pregnancies, ultrasound findings, prenatal investigations and interventions was obtained from the electronic ultrasound database, while data on placental histopathological findings, pregnancy outcome, mode of delivery, birth weight, gestational age at delivery and admission to the neonatal intensive care unit were obtained from maternity records. Categorical variables were compared using the chi-square or Fisher's exact test, while continuous variables were compared using the Student's t-test, ANOVA for multiple comparisons and the Kruskal-Wallis test. Of the 497 twin pregnancies included in the analysis, 351 (70.6%) were dichorionic and 146 (29.4%) were monochorionic. The incidence of birth-weight discordance of 25% or more was significantly higher in pregnancies with velamentous and those with marginal cord insertions compared to those with normal cord insertion (24.0%, 15.3% vs 7.6%, P< 0.001 and P= 0.020, respectively). In pregnancies with birth-weight discordance of 25% or more, the smaller twins had significantly higher prevalence of velamentous (13.8%) and marginal (34.2%) cord insertions compared with the larger twins (1.8% and 18.5%, respectively, P< 0.001). The smaller twins of the monochorionic diamniotic pregnancies showed an even higher prevalence of velamentous (29.5%) and marginal (40.9%) cord insertions compared with the larger twins (2.3% and 31.5%, respectively, P< 0.001). Compared with the normal cord insertion group, only velamentous insertion was associated significantly with the risk of sFGR (odds ratio (OR), 9.24 (95% CI, 2.05-58.84), P< 0.001) and birth-weight discordance of 20% or more (OR, 4.34 (95% CI, 1.36-14.61), P= 0.007) and 25% or more (OR, 6.81 (95% CI, 1.67-34.12), P= 0.003) in monochorionic twin pregnancies. There was no significant association between velamentous cord insertion and TTTS (P= 0.591), or between marginal cord insertion and the development of sFGR (P= 0.233), birth-weight discordance of 25% or more (P= 0.114) or TTTS (P= 0.487). Subgroup analysis of dichorionic twins showed that abnormal cord insertion was not associated with the risk of birth-weight discordance (P= 0.999), sFGR (P= 0.308), composite neonatal adverse outcome (P= 0.637) or intrauterine death (P= 0.349). Monochorionic twins with velamentous cord insertion are at increased risk of birth-weight discordance and sFGR. Sonographic delineation of placental cord insertion could be of value in the antenatal stratification of twin pregnancies. Prospective studies are required to assess the value and predictive accuracy of this potential screening marker. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

ObjectivesTo determine the prevalence of, and risk factors for anomalous insertions of the umbilical cord, and the risk for adverse outcomes of these pregnancies.DesignPopulation-based registry study.SettingMedical Birth Registry of Norway 1999–2009.PopulationAll births (gestational age >16 weeks to <45 weeks) in Norway (623,478 singletons and 11,263 pairs of twins).MethodsDescriptive statistics and odds ratios (ORs) for risk factors and adverse outcomes based on logistic regressions adjusted for confounders.Main outcome measuresVelamentous or marginal cord insertion. Abruption of the placenta, placenta praevia, pre-eclampsia, preterm birth, operative delivery, low Apgar score, transferral to neonatal intensive care unit (NICU), malformations, birthweight, and perinatal death.ResultsThe prevalence of abnormal cord insertion was 7.8% (1.5% velamentous, 6.3% marginal) in singleton pregnancies and 16.9% (6% velamentous, 10.9% marginal) in twins. The two conditions shared risk factors; twin gestation and pregnancies conceived with the aid of assisted reproductive technology were the most important, while bleeding in pregnancy, advanced maternal age, maternal chronic disease, female foetus and previous pregnancy with anomalous cord insertion were other risk factors. Velamentous and marginal insertion was associated with an increased risk of adverse outcomes such as placenta praevia (OR = 3.7, (95% CI = 3.1–4.6)), and placental abruption (OR = 2.6, (95% CI = 2.1–3.2)). The risk of pre-eclampsia, preterm birth and delivery by acute caesarean was doubled, as was the risk of low Apgar score, transferral to NICU, low birthweight and malformations. For velamentous insertion the risk of perinatal death at term was tripled, OR = 3.3 (95% CI = 2.5–4.3).ConclusionThe prevalence of velamentous and marginal insertions of the umbilical cord was 7.8% in singletons and 16.9% in twin gestations, with marginal insertion being more common than velamentous. The conditions were associated with common risk factors and an increased risk of adverse perinatal outcomes; these risks were greater for velamentous than for marginal insertion.

INTRODUCTION: Fetomaternal hemorrhage (FMH) and placental abruption may both result in adverse fetal and neonatal outcomes but have differing pathophysiology. Abruption reportedly can lead to small volume FMH, but a positive test for FMH does not indicate a diagnosis of abruption. METHODS: We performed a case-control study within Kaiser Northern California (2008–2017), first identifying all cases of FMH within this time period (defined as a positive flow cytometry for fetal hemoglobin and adverse fetal or neonatal outcomes related to hypovolemia). Cases of FMH were compared to matched controls from the same delivery cohort. We reviewed delivery records and placental pathology reports to identify whether placental abruption was clinically suspected. RESULTS: Our study included 56 women in the FMH group and 132 in the control group. Concern for placental abruption was noted in 10.6% of those without FMH and in 12.5% of those with FMH, with no significant difference between the two groups (P=.71). The adjusted odds ratio was 1.33 (95% CI .49–3.62) after adjusting for maternal age and maternal race/ethnicity. CONCLUSION: Placental abruption is not more likely to occur in clinically significant FMH compared to other deliveries for which placental pathology is obtained. Obstetric providers should consider FMH and abruption as separate clinical entities. Flow cytometry for fetal hemoglobin should be ordered in the setting of clinical suspicion for FMH, unexplained intrauterine fetal death, or adverse outcomes related to fetal or neonatal hypovolemia. The Kleihauer-Betke and flow cytometry tests for fetal hemoglobin do not confirm or refute the possibility of abruption.

In vitro fertilization is a risk factor for vasa previa

Severe fetomaternal hemorrhage (FMH) is a rare but potentially life-threatening perinatal complication (1). The traditional method for diagnosis of this situation is the acid elution (Kleihaur–Betke) test. However, this technique is relatively insensitive and non-specific, and does not allow quantification of the hemorrhagic process. We report a case of severe FMH confirmed and quantified by means of flow cytometric analysis using specific staining for cells containing fetal hemoglobin (HbF) in maternal circulation. We believe that this method is more sensitive, more specific and allows accurate quantification of FMH. A 30-year-old nullipara at 36 + 2 gestational weeks was admitted to the delivery room for decreased fetal movements. On admission, a sinusoidal fetal heart rate pattern was recorded (Fig. 1), and an immediate cesarean section was performed. A 2400 g female infant was delivered with Apgar scores of five and seven at 1 and 5 min, respectively. The infant was extremely pale, limp and bradycardic. Initial hematocrit and hemoglobin levels were 12.3% and 4.4 g/dL, respectively, while a direct Coombs' test was negative. She was treated initially by infusion of normal saline followed by packed red blood cells (20 cc/kg), until marked clinical improvement, and her hematocrit reached 35%. The rest of her postnatal course was unremarkable. Fetal cardiotogoram showing a sinusoidal fetal heart rate pattern. In an attempt to confirm the suspected diagnosis of FMH, we performed flow cytometric analysis of fetal erythrocytes in maternal blood samples obtained soon after delivery. The cells were washed, fixed permiabilized and stained with monoclonal antibodies against HbF according to the manufacturer's instructions (Bioatlantic, Nantes, France). Cell analysis was performed with a FACstarplus flow cytometer (Beckton-Dickenson, Mountain View, CA, USA). A 488-nm argon laser beam at 250 mV served for excitation. The threshold was set on forward light scatter to exclude platelets. Green fluorescence was measured using logarithmic amplification through a 530 ± 30 nm band-pass-filter. As a positive control we used 3 neonatal cord blood samples and as negative controls blood samples from five other women after normal deliveries. The positivity threshold was adjusted with positive controls. Almost 11% of maternal erythrocytes contained high HbF level, i.e. were of fetal origin (Fig. 2). These results were confirmed by analyzing the hemoglobin types in the hemolysate of the maternal blood using high performance liquid chromatography (results not shown). Histogram of flow cytometric analysis of three samples stained for HbF. The flourescence intensity is demonstrated on a log scale along the X-axis, and the cell count along the Y-axis. A. The presented case showing a major peak of HbF negative cells (maternal cells) and a minor peak of cells containing high levels of HbF, i.e, fetal cells. B. A sample of umbilical cord blood. C. A sample of control maternal blood. Detection of fetal cells in maternal circulation represents an important support for the clinical diagnosis of FMH. Most laboratories perform FMH estimates on the basis of the slide-based microscopic counting method of acid elution (Kleihaur–Betke) test. This technique is laborious and suffers from lack of sensitivity, subjectivity and precision (2). These limitations prompted the use of flow cytometry which overcomes all these limitations by rapid and sensitive cell-by-cell analysis (3). In the past, flow cytometry approaches of fetal cells in maternal blood relied mainly on detection of the human D antigen. However, this approach was applicable only to clinical situations with D antigen incompatibility and could not be utilized in all cases of FMH. Using antibodies to HbF as described in the current case allows for broad application to various clinical situations (4, 5). Moreover, the quantitative nature of flow cytometric analysis permits the distinction of true fetal cells, which contain HbF as the major form of hemoglobin, from maternal circulating F-cells that have lower cellular HbF content. This is particularly applicable for individuals with hereditary persistence of HbF or various hemoglobinopathies. To our knowledge, this is the first reported case of severe FMH confirmed and quantified by flow cytometry using anti HbF antibodies. Clinicians may wish to apply this rapid and accurate method for diagnostic purposes postnataly and even antenatally when clinical suspicion arises.

Two cases of asymptomatic massive fetomaternal hemorrhage

Hemorrhage is one of the major causes of maternal death. Main causes of APH are placenta previa, placenta abruption and uterine rupture. Rare causes of placenta abruption include marginal and velamentous umbilical cord insertions. We hereby present a case of placenta abruption due to marginal umbilical cord insertions occurring on a bipartite placenta. A 40-year-old nulliparous African woman, 35 weeks pregnant consulted for dark red pervaginal bleeding, which occurred recently. Past history was unremarkable. Her pregnancy was well followed up. A recent ultrasound scan revealed a fundal inserted placenta. Physical examination revealed a fundal height of 37 cm, no uterine activity, normal fetal heart tones and a blood-stained vulva. Our diagnosis was a mild placenta abruption. An obstetrical ultrasound carried out revealed a normal pregnancy and a retroplacental blood clot of 11mm. A safe baby was born through an emergency cesarean section which revealed a normally inserted bipartite placenta with a 10% placenta detachment located on one placenta half and two cords inserted marginally. The postoperative period was uneventful and she was discharged five days after cesarean section. This case report shows that marginal cord insertion, which can lead to placenta abruption, can be also observed on a bipartite placenta.

We sought to evaluate the associations between umbilical artery pH and base excess and neurodevelopmental outcome at four years of age. This study comprised 84588 singleton children born alive at term in 2005-2011 in the hospital district of Helsinki and Uusimaa in Finland. Data from the maternity hospital information system were linked to the data from the Medical Birth Register and the Hospital Discharge Register. Neurodevelopmental morbidity included cerebral palsy, epilepsy, intellectual or sensorineural impairment. After adjustment for maternal and perinatal factors, a combination of pH <7.00 and base excess <-16.00 was associated with infant death (adjusted odds ratio 19.97; 95% confidence interval 5.38-74.17). Values of pH 7.00-7.10 were associated with cerebral palsy (adjusted odds ratio 2.40; 95% confidence interval 1.05-5.47). A combination of low five-minute Apgar score and umbilical artery base excess <-16.00 showed the highest positive predictive value (9.1%) for neurodevelopmental impairments. When umbilical artery pH <7.00 was included, a positive predictive value of 25.0% was observed for infant mortality. Low umbilical artery pH and base excess at birth were the poor predictors of long-term neurodevelopmental morbidity in an unselected population. However, these parameters might be useful in assessing the risk of infant mortality.

Introduction/PurposeIt is well‐documented in the literature that the placenta migrates during pregnancy; however, studies regarding placental cord insertion (PCI) migration are scarce. This longitudinal, prospective study aimed to determine whether PCI migration is a true phenomenon, to assess whether the PCI can change classification during pregnancy and to determine the validity of PCI site documentation including follow‐up of abnormal PCI.MethodsEighty‐three participants who had first, second and third trimester ultrasound examinations at a Western Australian private imaging practice over a 12‐month period between November 2021 and November 2022 were recruited. The measured distance of the lower margin of the placenta to the cervix, the distance of the PCI to the closest placental edge and the PCI classification were documented in each trimester. Data analysis was conducted to determine PCI migration rates during pregnancy and to test for association between PCI migration and maternal and placental factors.ResultsThe PCI migrated during pregnancy and the PCI classification has the potential to evolve. All identifiable PCIs that were normal in first trimester remained so throughout the pregnancy. The majority (67.6%) of cord insertions that were marginal in first trimester progressed to a normal insertion site by third trimester; 23.5% remained marginal and 8.8% evolved to a velamentous insertion. Three velamentous cord insertions were recorded in first trimester, none of which normalised—two remained velamentous during the pregnancy and one evolved to marginal in second trimester. Marginal cord insertions (MCIs) ≤10 mm from the placental edge in second trimester remained marginal in third trimester; MCIs that were >15 mm from the placental edge in second trimester normalised in third trimester.ConclusionsPlacental cord insertion migration is a phenomenon that occurs during pregnancy with the potential for PCI classification to evolve. Due to the association between abnormal PCI and perinatal complications, coupled with the potential for marginal cord insertion to evolve, documentation of PCI and follow‐up of abnormal PCI is beneficial, particularly in cases of velamentous insertion and marginal insertion at the placental edge or in the lower uterus.

Prevalence of velamentous and marginal umbilical cord insertions; a comparison of term singleton ART and non-ART pregnancies

ABSTRACTObjectivesCerebral palsy (CP) is a group of movement disorders usually diagnosed in childhood. A substantial proportion are thought to be caused by antenatal events. Abnormalities of the umbilical cord and placenta are associated with an increased risk of adverse neonatal outcomes, but it is unclear whether these conditions also carry an increased risk of CP. We aimed to determine whether abnormalities of the umbilical cord or placenta are associated with CP and assess if these associations differ by sex of the child or gestational age at birth.MethodsWe performed a national cohort study by linking data from The Medical Birth Registry of Norway with other national registries. All liveborn singletons born between 1999 and 2017 (n = 1 087 486) were included and followed up until the end of 2019. Diagnoses of CP were provided by the Norwegian National Insurance Scheme and the Norwegian Patient Register. We used generalized estimating equations and multilevel log binomial regression to calculate relative risks (RR), adjusted for year of birth, and stratified analyses were carried out based on sex and gestational age at birth. Exposures were abnormal umbilical cord (velamentous or marginal insertion, single umbilical artery (SUA), knots and entanglement), and placental abnormalities (retained placenta, placental abruption and previa).ResultsA total of 2443 cases with CP (59.8% males) were identified. Velamentous cord insertion (adjusted RR (aRR), 2.11 (95% CI, 1.65–2.60)), cord knots (aRR, 1.53 (95% CI, 1.15–2.04)) and placental abnormalities (placenta previa (aRR, 3.03 (95% CI, 2.00–4.61)), placental abruption (aRR, 10.63 (95% CI, 8.57–13.18)) and retained placenta (aRR, 1.71 (95% CI, 1.32–2.22))) carried an increased risk of CP. Velamentous cord insertion was associated with CP regardless of gestational age or sex. A retained placenta was associated with a 2‐fold increased risk for CP in males, while the associations of SUA and cord knot with CP were significant only among females.ConclusionsThe detection of placental and umbilical cord abnormalities may help identify children at increased risk of CP. The associations between placental or umbilical cord abnormalities and the risk of CP do not vary substantially with gestational age at birth or sex of the child. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The nature of structural defects associated with velamentous and marginal insertion of the umbilical cord

Placental abruption is a major obstetrical complication bearing potentially life-threatening consequences. Though the diagnosis of placental abruption is a clinical one, the nonspecific nature of common presenting symptoms, mainly vaginal bleeding and contractions, pose a challenge, and the contribution of placental pathology has been debated. In this study, we assessed the clinical significance of related placental lesions by comparing obstetric and neonatal outcomes among cases of placental abruption with versus without supporting histopathologic placental lesions. We retrospectively analyzed placental abruption cases diagnosed during an 8-year period at a single tertiary center. Maternal, neonatal, and placental outcomes were compared between cases of placental abruption with versus without histopathologic placental lesions. The primary outcome was a composite of severe neonatal morbidity and included 1 ≤ of the following: seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, blood transfusion or neonatal death. A total of 305 clinical placental abruption cases were included: 95 in the placental abruption with histopathologic lesions group (31.3%) and 210 without such lesions (68.8%). The group with histopathologic lesions was characterized by higher rates of vaginal bleeding at presentation and prematurity (P = 0.012 and P < 0.001, respectively). Additionally, this group had substantially higher rates of composite severe neonatal outcomes (the primary outcome) (P = 0.005) and concurrent maternal vascular malperfusion lesions (P < 0.001). Our findings shed light on the association between placental abruption-related histopathologic lesions and adverse obstetric and neonatal outcomes. Thus, histopathologic examination can be advocated in suspected placental abruption, as patients with related placental lesions may require closer follow-up in subsequent pregnancies.

The aim of this study was to determine the perinatal outcomes of placental abruption associated with the presence of histological chorioamnionitis. We reviewed the obstetric records of 96 singleton deliveries complicated by placental abruption after 22 weeks' gestation. Of these 96 cases, 37 cases (39%) were diagnosed as having histological chorioamnionitis in the placenta. The incidence of premature delivery, preterm rupture of the membranes and low birth weight in the cases of placental abruption with chorioamnionitis were higher than in cases without chorioamnionitis. However, there were no significant differences in the incidence of other outcomes, such as fetal demise, low Apgar score, or low umbilical artery pH, between the cases of placental abruption with and without histological chorioamnionitis. Although the incidence of prematurity in the cases of placental abruption with chorioamnionitis was higher than that in cases without chorioamnionitis, there were no significant differences in fetal and neonatal conditions between the abruption cases with and without chorioamnionitis.