The Outcome after Laser Therapy of Monochorionic Twin Pregnancies Complicated by Twin-Twin Transfusion Syndrome with Coexistent Selective Fetal Growth Restriction.

Background: Most previous studies evaluated outcomes of twin-twin transfusion syndrome (TTTS) without considering the coexistence of selective fetal growth restriction (sFGR). The objectives of this study were to compare twin survival and pregnancy complications after laser therapy of TTTS with and without sFGR. Methods: For this purpose, a retrospective cohort study including 98 monochorionic diamniotic twins and three dichorionic triamniotic triplets treated in a single tertiary center was conducted. Results: Overall, 46 twins had selective fetal growth restriction (26 type I, 13 type II, 7 type III). At birth, donor survival (61% vs. 91%), double survival (57% vs. 82%), and overall survival (75% vs. 88%) were significantly lower in the group with coexistent sFGR. Recipient survival (89% vs. 86%), miscarriage (7% vs. 2%), PPROM < 32 weeks (48% vs. 29%), and preterm delivery < 32 weeks (52% vs. 45%) were not significantly higher in the group with coexistent sFGR. Donor twins with sFGR type I (69% vs. 91%) and types II-III (50% vs. 91%) showed significantly lower survival than those without sFGR. Multivariate regression analysis identified sFGR and its subtypes as independent predictors of donor demise. Conclusions: the coexistence of sFGR in TTTS pregnancies was associated with poor donor outcomes and is probably the most important predictor of donor survival.

Comparison of phase rectified signal averaging and short term variation in predicting perinatal outcome in early onset fetal growth restriction.

OBJECTIVES: To compare short term variation (STV) and phase rectified signal averaging (PRSA) and their association with fetal outcome in early onset fetal growth restriction (FGR). METHODS: Data were used from a retrospective cohort study of women who were admitted for FGR and/or pre-eclampsia and who were delivered by pre-labor Cesarean section or had a fetal death before 32 weeks' gestation. Computerized cardiotocography (cCTG) registrations of the 5 days before delivery or fetal death were used for calculation of STV and PRSA. PRSA was expressed as the average acceleration capacity (AAC) and average deceleration capacity (ADC). FHR decelerations were classified visually as absent, 1-2 per hour or recurrent. Abnormality of STV and of PRSA was either analyzed as a single parameter or in combination with recurrent decelerations. Endpoints were defined as composite adverse condition at birth consisting of fetal death, low Apgar score, low umbilical pH, the need for resuscitation after birth and as major neonatal morbidity or neonatal death. RESULTS: Included were 367 pregnancies of which 20 resulted in fetal death. An abnormal cCTG with either recurrent decelerations and/or low STV or recurrent decelerations and/or low PRSA were similarly associated with composite adverse condition at birth (n=99), but neither with major neonatal morbidity. CONCLUSIONS: PRSA and STV have similar efficacy for measuring fetal heart rate variation in early onset FGR. An increased risk of a composite adverse condition at birth is indicated by a low value of either parameter and/or the presence of recurrent decelerations.

Prognostic Value of Cerebroplacental Ratio in Appropriate-for-Gestational-Age Fetuses Before Induction of Labor in Late-Term Pregnancies.

PURPOSE: To evaluate the relationship between cerebroplacental ratio (CPR) and the need for operative delivery due to intrapartum fetal compromise (IFC) and adverse perinatal outcome (APO) in appropriate-for-gestational-age (AGA) late-term pregnancies undergoing induction of labor. The predictive performance of CPR was also assessed. MATERIALS AND METHODS: Retrospective study including singleton AGA pregnancies that underwent elective induction of labor between 41 + 0 and 41 + 6 weeks and were delivered before 42 + 0 weeks. IFC was defined as persistent pathological CTG or pathological CTG and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery (IVD) and cesarean section (CS). APO was defined as a composite of umbilical artery pH < 7.20, Apgar score < 7 at 5 minutes, and admission to the neonatal intensive care unit for > 24 hours. RESULTS: The study included 314 women with 32 (10 %) IVDs and 49 (16 %) CSs due to IFC and 85 (27 %) APO cases. Fetuses with CPR < 10th percentile showed a significantly higher rate of operative delivery for IFC (40 % (21/52) vs. 23 % (60/262); p = 0.008) yet not a significantly higher rate of APO (31 % (16/52) vs. 26 % (69/262); p = 0.511). The predictive values of CPR for operative delivery due to IFC and APO showed sensitivities of 26 % and 19 %, specificities of 87 % and 84 %, positive LRs of 2.0 and 1.2, and negative LRs of 0.85 and 0.96, respectively. CONCLUSION: Low CPR in AGA late-term pregnancies undergoing elective induction of labor was associated with a higher risk of operative delivery for IFC without increasing the APO rate. However, the predictive value of CPR was poor.

Perinatal Outcome and its Prediction Using Longitudinal Feto-Maternal Doppler Follow-Up in Late Onset Small for Gestational Age Fetuses - A Prospective Cohort Study.

PURPOSE: To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. METHODS: Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. RESULTS: A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p < 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63). CONCLUSION: SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.

Value of Cerebroplacental Ratio and Uterine Artery Doppler as Predictors of Adverse Perinatal Outcome in Very Small for Gestational Age at Term Fetuses.

The aim of this study was to evaluate the association between cerebroplacental ratio (CPR), mean uterine artery (mUtA) Doppler and adverse perinatal outcome (APO) and their predictive performance in fetuses with birth weight (BW) <3rd centile (very small for gestational age, VSGA) in comparison with fetuses with BW 3rd−10th centile (small for gestational age, SGA). This was a retrospective cohort study including singleton pregnancies delivered at term (37 + 0−41 + 6) in a single tertiary referral center over a six-year period. APO was defined as a composite of cesarean section for intrapartum fetal compromise (IFC), umbilical artery pH < 7.20, and admission to the neonatal intensive care unit for >24 h. The characteristics of the study population according to BW (VSGA and SGA) as well as the presence of composite APO were assessed. The prognostic performance of CPR and mUtA-PI was evaluated using receiver operating characteristic (ROC) analysis. In total, 203 pregnancies were included. Of these, 55 (27%) had CPR <10th centile, 25 (12%) mUtA-PI >95th centile, 65 (32%) VSGA fetuses, and 93 (46%) composite APO. VSGA showed a non-significantly higher rate of composite APO in comparison to SGA (52% vs. 43%; p = 0.202). The composite APO rate was significantly higher in SGA with CPR <10th centile (36% vs. 13%; p = 0.001), while in VSGA with CPR <10th centile was not (38% vs. 35%; p = 0.818). The composite APO rate was non-significantly higher both in VSGA (26% vs. 10%; p = 0.081) and SGA (14% vs. 6%; p = 0.742) with mUtA-PI >95th centile. The ROC analysis showed a significantly predictive value of CPR for composite APO in SGA only (AUC 0.612; p = 0.025). A low CPR was associated with composite APO in SGA fetuses. VSGA fetuses were more frequently affected by composite APO regardless of Doppler values. The predictive performance of CPR and uterine artery Doppler was poor.

Maternal-fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study.

BACKGROUND: Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant's neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA. RESULTS: A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a 'Fetal Stress Index' (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn's saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. CONCLUSIONS: Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

Performance of sFlt-1/PIGF Ratio for the Prediction of Perinatal Outcome in Obese Pre-Eclamptic Women.

Obese women are at high risk of developing pre-eclampsia (PE). As an altered angiogenic profile is characteristic for PE, measurement of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PIGF) ratio in the maternal serum can be helpful for PE diagnosis, as well as for adverse perinatal outcome (APO) prediction. There is growing evidence that obesity might influence the level of sFlt-1/PIGF and, therefore, the aim of the study was the evaluation of sFlt-1/PIGF as an APO predictor in obese women with PE. Pre-eclamptic women who had an sFlt-1/PIGF measurement at the time of diagnosis were retrospectively included. Women were classified according to their pre-pregnancy body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI > 25−29.9 kg/m2) or obese (BMI ≥ 30 kg/m2). APO was defined as the occurrence of one of the following outcomes: Small for gestational age, defined as a birthweight < 3rd centile, neonatal mortality, neonatal seizures, admission to neonatal unit required (NICU) or respiratory support. A total of 141 women were included. Of them, 28 (20%) patients were obese. ROC (receiver operating characteristic) analysis revealed a high predictive value for sFlt-1/PIGF and APO across the whole study cohort (AUC = 0.880, 95% CI: 0.826−0.936; p < 0.001). However, the subgroup of obese women showed a significantly lower level of sFlt-1 and, therefore, the performance of sFlt-1/PIGF as APO predictor was poorer compared to normal or overweight PE women (AUC = 0.754, 95% CI: 0.552−0.956, p = 0.025). In contrast to normal or overweight women, a ratio of sFlt-1/PIGF < 38 could not rule out APO in women with obesity.

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner.

The adverse effects of maternal prenatal stress (PS) on child's neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

Impact of Preoperative Cervical Length on Pregnancy Outcome in Twin-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the impact of preoperative cervical length on pregnancy outcome in monochorionic diamniotic twin pregnancies complicated by twin-twin transfusion syndrome that underwent laser surgery or cord occlusion. MATERIALS AND METHODS: Retrospective study of 330 patients stratified by preoperative cervical length (≥25 mm, 16-24 mm,≤15 mm). Maternal characteristics, operative data, and pregnancy outcomes were compared between the cervical length groups as well as between the subgroups of patients with a cervical length≤15 mm according to management (expectant vs. cerclage). RESULTS: A preoperative cervical length≥25 mm was observed in 82% (n=271) of cases, 16-24 mm in 9% (n=29), and≤15 mm in 9% (n=30). Patients with a preoperative cervical length≤15 mm showed shorter median procedure-to-delivery interval (5.5 weeks vs. 11.6 (16-24 mm) vs. 13.0 (≥25 mm); p<0.001); lower median gestational age at delivery (29.5 weeks vs. 34.3 (16-24 mm) vs. 33.4 (≥25 mm); p<0.001); higher rate of preterm delivery<32 weeks (78 vs. 20% (16-24 mm) vs. 31% (≥25 mm); p<0.001); and lower neonatal survival rate of at least one twin (70 vs. 88% (16-24 mm) vs. 93% (≥25 mm); p<0.001). Outcome of patients with a preoperative cervical length≤15 mm was similar regardless of management. CONCLUSION: Monochorionic diamniotic twin pregnancies complicated by twin-twin transfusion syndrome with a preoperative cervical length≤15 mm showed a higher rate of preterm delivery<32 weeks and lower neonatal survival. The role of a cervical cerclage remains unclear.

Hepatitis E, Schistosomiasis and Echinococcosis-Prevalence in a Cohort of Pregnant Migrants in Germany and Their Influence on Fetal Growth Restriction.

BACKGROUND: Infections, as well as adverse birth outcomes, may be more frequent in migrant women. Schistosomiasis, echinococcosis, and hepatitis E virus (HEV) seropositivity are associated with the adverse pregnancy outcomes of fetal growth restriction and premature delivery. METHODS: A cohort study of 82 pregnant women with a history of migration and corresponding delivery of newborns in Germany was conducted. RESULTS: Overall, 9% of sera tested positive for anti-HEV IgG. None of the patients tested positive for anti-HEV IgM, schistosomiasis, or echinococcus serology. Birth weights were below the 10th percentile for gestational age in 8.5% of the neonates. No association between HEV serology and fetal growth restriction (FGR) frequency was found. CONCLUSIONS: In comparison to German baseline data, no increased risk for HEV exposure or serological signs of exposure against schistosomiasis or echinococcosis could be observed in pregnant migrants. An influence of the anti-HEV serology status on fetal growth restriction could not be found.

Cardiovascular outcome of former late-onset small-for-gestational-age children at 1 year of age: CURIOSA study.

OBJECTIVE: Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year. METHODS: We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included. RESULTS: A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0-4 months vs. > 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown. CONCLUSION: Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children.

Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study.

OBJECTIVES: An association between fetal growth restriction (FGR) and increased predisposition to cardiovascular disease (CVD) is suggested. The aim of this study was to evaluate subclinical signs of fetal cardiac remodeling in late-onset small-for-gestational-age (SGA) and growth-restricted fetuses using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: This is a prospective cohort study, including 117 late-onset (≥32 weeks) SGA (birthweight≤10th centile) fetuses and 102 gestational age matched controls. A subgroup analysis was performed: FGR was defined based on either BW (0.05). Regarding global and segmental LPSS and LSR values of LV/RV, subgroup analysis revealed no significant difference between the FGR (n=81), SGA centile 3-10 (n=36) and control group. CONCLUSIONS: A mild degree of placental dysfunction seems not to influence myocardial deformation properties measured by 2D-STE.

Early Biomarkers and Intervention Programs for the Infant Exposed to Prenatal Stress.

Functional development of affective and reward circuits, cognition and response inhibition later in life exhibits vulnerability periods during gestation and early childhood. Extensive evidence supports the model that exposure to stressors in the gestational period and early postnatal life increases an individual's susceptibility to future impairments of functional development. Recent versions of this model integrate epigenetic mechanisms of the developmental response. Their understanding will guide the future treatment of the associated neuropsychiatric disorders. A combination of non-invasively obtainable physiological signals and epigenetic biomarkers related to the principal systems of the stress response, the Hypothalamic-Pituitary axis (HPA) and the Autonomic Nervous System (ANS), are emerging as the key predictors of neurodevelopmental outcomes. Such electrophysiological and epigenetic biomarkers can prove to timely identify children benefiting most from early intervention programs. Such programs should ameliorate future disorders in otherwise healthy children. The recently developed Early Family-Centered Intervention Programs aim to influence the care and stimuli provided daily by the family and improving parent/child attachment, a key element for healthy socio-emotional adult life. Although frequently underestimated, such biomarker-guided early intervention strategy represents a crucial first step in the prevention of future neuropsychiatric problems and in reducing their personal and societal impact.

Left myocardial performance index in monochorionic diamniotic twin pairs complicated by selective fetal growth restriction with abnormal umbilical artery Doppler.

OBJECTIVE: To evaluate left myocardial performance index (MPI) and its time intervals in monochorionic diamniotic (MCDA) twin pairs complicated by selective fetal growth restriction (sFGR) with abnormal (persistent -type II- or intermittent -type III- absent or reversed end-diastolic flow) umbilical artery Doppler. METHODS: Retrospective study including 16 MCDA twin pairs with sFGR type II, 26 MCDA twin pairs with sFGR type III and 42 gestational age-matched uncomplicated MCDA twin pairs in a single tertiary center. Left isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured and MPI calculated by conventional Doppler at diagnosis of sFGR. RESULTS: In sFGR type II, the smaller twin had shorter ET and prolonged IRT and MPI, while the larger twin showed prolonged ICT and MPI as compared to uncomplicated MCDA twins. In sFGR type III, the smaller twin had shorter ICT and ET, while the larger twin showed prolonged ICT, IRT, and MPI in comparison to controls. CONCLUSION: A differential pattern of MPI time intervals could be observed in MCDA twins with sFGR type II and III. All twins had echocardiographic signs of pressure/volume overload, except the smaller twin type III with shorter systolic times probably reflecting reduced volume load.

Does gestational age at term play a role in the association between cerebroplacental ratio and operative delivery for intrapartum fetal compromise?

INTRODUCTION: To assess the impact of gestational age at term on the association between cerebroplacental ratio (CPR) and operative delivery for intrapartum fetal compromise (IFC) and prognostic performance of CPR to predict operative delivery for IFC. MATERIAL AND METHODS: This was a retrospective cohort study including 2052 singleton pregnancies delivered between 37+0 and 41+6  weeks of gestation in a single tertiary referral center over an 8-year period. CPR was measured within 1 week of delivery. IFC was defined as the presence of persistent pathological cardiotocography pattern or the combination of pathological cardiotocography pattern and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery and cesarean section. Pregnancies were grouped according to birthweight (small for gestational age [SGA, birthweight <10th centile] and appropriate for gestational age [AGA, birthweight 10th-90th centile]) and gestational age by week at delivery. Rates of operative delivery were compared between the subgroups. Prognostic value of CPR was assessed using receiver operating characteristic curve. RESULTS: Of the study cohort, 308 (15%) had a CPR <10th centile, 374 (18%) operative delivery for IFC, and 298 (15%) were SGA at birth. Overall, the rates of operative delivery for IFC were higher in the low CPR group both in SGA (35% vs. 22%; p = 0.023) and in AGA (23% vs. 16%; p = 0.007). According to gestational age by week at delivery, fetuses with low CPR showed higher rates of operative delivery for IFC with advancing gestational age, mainly in pregnancies delivered at 40 weeks (54% vs. 23%; p = 0.004) and at 41 weeks (60% vs. 19%; p = 0.010) for SGA and at 41 weeks (39% vs. 20%; p = 0.001) for AGA. The predictive value of CPR remained stable throughout term and was poor both in SGA and in AGA. CONCLUSIONS: Both SGA and AGA fetuses with low CPR showed higher rates of operative delivery for IFC at term with advancing gestational age. Prognostic value of CPR throughout term was poor.

Prediction of adverse perinatal outcome and the mean time until delivery in twin pregnancies with suspected pre-eclampsia using sFlt-1/PIGF ratio.

PURPOSE: An elevated soluble fms-like tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) ratio is associated with adverse perinatal outcome (APO) and the mean time until delivery (MTUD) in singleton pregnancies complicated by pre-eclampsia (PE). Data on APO and MTUD prediction in twin pregnancies using sFlt-1/PlGF ratio are scarce. We evaluated the predictive value of the sFlt-1/PIGF ratio regarding APO and MTUD in twin pregnancies with suspected PE and/or HELLP syndrome. METHODS: This is a single center retrospective cohort study. All twin pregnancies with suspected PE/HELLP and determined sFlt-1/PIGF were included. Composite APO (CAPO) was defined as the presence of at least one of the following outcomes: respiratory distress syndrome (RDS), intubation, admission to neonatal intensive care unit (NICU) and arterial umbilical cord pH value < 7.10. Selective fetal growth restriction (s-FGR) was analyzed separately. RESULTS: For final analysis, 49 twin pregnancies were included. Median sFlt-1/PIGF ratio was not significantly different in patients with CAPO compared to those without (89.45 vs. 62.00, p = 0.669). MTUD was significantly negative correlated with sFlt-1/PIGF ratio (r = -0.409, p < 0.001). For the whole study cohort, ROC analysis revealed no predictive value for sFlt-1/PIGF and CAPO (AUC = 0.618, 95% CI: 0.387-0.849, p = 0.254). However, sFlt-1/PIGF ratio showed a predictive value for s-FGR (AUC = 0.755, 95% CI: 0.545-0.965, p = 0.032). CONCLUSION: In twin pregnancies with PE and/or HELLP, sFlt-1/PIGF ratio may be helpful for s-FGR prediction and decision-making regarding close monitoring of high-risk patients. However, further prospective studies are warranted to define the role of sFlt-1/PlGF ratio as outcome predictor in twin pregnancies.

Fetal growth restriction in a cohort of migrants in Germany.

BACKGROUND: Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction / fetal growth restriction (IUGR/FGR) in pregnant migrants. METHOD: Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany. RESULTS: The Median age was 27 years, 49% of patients were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76% of patients, in 40% the delivery mode was caesarian section. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1% of pregnancies. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (< 2500 g) occurred in 6.1%. Birth weights below the 10th percentile of birth weight for gestational age were observed in 8.5% of the total cohort. CONCLUSIONS: Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR/FGR was found. We note that the rate of caesarian section births was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.

Spine surgery in pregnant women: a multicenter case series and proposition of treatment algorithm.

PURPOSE: Spinal diseases requiring urgent surgical treatment are rare during pregnancy. Evidence is sparse and data are only available in the form of case reports. Our aim is to provide a comprehensive guide for spinal surgery on pregnant patients and highlight diagnostic and therapeutic aspects. METHODS: The study included a cohort of consecutive pregnant patients who underwent spinal surgery at five high-volume neurosurgical centers between 2010 and 2017. Perioperative and perinatal clinical data were derived from medical records. RESULTS: Twenty-four pregnant patients were included. Three underwent a preoperative cesarean section. Twenty-one patients underwent surgery during pregnancy. Median maternal age was 33 years, and median gestational age was 13 completed weeks. Indications were: lumbar disk prolapse (n = 14; including cauda equina, severe motor deficits or acute pain), unstable spine injuries (n = 4); intramedullary tumor with paraparesis (n = 1), infection (n = 1) and Schwann cell nerve root tumor presenting with high-grade paresis (n = 1). Two patients suffered transient gestational diabetes and 1 patient presented with vaginal bleeding without any signs of fetal complications. No miscarriages, stillbirths, or severe obstetric complications occurred until delivery. All patients improved neurologically after the surgery. CONCLUSION: Spinal surgical procedures during pregnancy seem to be safe. The indication for surgery has to be very strict and surgical procedures during pregnancy should be reserved for emergency cases. For pregnant patients, the surgical strategy should be individually tailored to the mother and the fetus.

Can fetal heart rate variability obtained from cardiotocography provide the same diagnostic value like from electrophysiological interbeat intervals?

OBJECTIVE: Fetal heart rate variability (HRV) is widely used for monitoring fetal developmental disturbances. Only expensive fetal magnetocardiography (fMCG) allows the precise recording of the individual fetal heart beat intervals uncovering also highly frequent vagal modulation. In contrast, transabdominal fetal electrocardiography (fECG) suffers from noise overlaying the fetal cardiac signal. Cardiotocography (CTG) is the clinical method of choice, however, based on Doppler ultrasound, improper to resolve single beats concisely. The present work addresses the transferability of established electrophysiological HRV indices to CTG recordings during the fetal maturation period of 20-40 weeks of gestation (WGA). APPROACH: We compared (a) HRV indices obtained from fMCG, CTG and fECG of short-term amplitude fluctuations (sAMPs) and long-term amplitude fluctuations (lAMPs) and complexity, and (b) their diagnostic value for identifying maturational age, fetal growth restriction (FGR) and small for gestational age (SGA). We used the functional brain age score (fABAS) and categories of long- and short-term regulation and complexity. MAIN RESULTS: Integrating all substudies, we found: (a) indices related to long-term regulation, and with modified meaning and values of short-term regulation and sympathovagal balance (SVB) according to electrophysiological HRV standards can be obtained from CTG. (b) Models using HRV indices calculated from CTG allow the identification of maturational age and discriminate FGR from controls with almost similar precision as electrophysiological means. (c) A modified set of HRV parameters containing short- and long-term regulation and long-term/short-term ratio appeared to be most suitable to describe autonomic developmental state when CTG data is used. SIGNIFICANCE: Whereas the predominantly vagally modulated beat-to-beat precise high frequencies of HRV are not assessable from CTG, we identified relevant related HRV indices and categories for CTG recordings with diagnostic potential. They require further evaluation and confirmation with respect to any issues of fetal developmental and perinatal problems in subsequent studies. This methodology significantly extends the measures of established CTG devices. Novelty and significance HRV indices provide predestinated diagnostic markers of autonomic control in fetuses. However, the established CTG does not provide the temporal precision of electrophysiological recordings. Beat-to-beat related, mainly vagally modulated behavior is not exactly represented in CTG. However, a set of CTG-specific HRV indices that are mainly comparable to established electrophysiological HRV parameters obtained by magnetocardiography or electrocardiography provided almost similar predictive value for fetal maturational age and were helpful in characterizing FGR. These results require validation in the monitoring of further fetal developmental disturbances. We recommend a corresponding extension of CTG methodology.

Role of sFlt-1/PIGF ratio and uterine Doppler in pregnancies with chronic kidney disease suspected with Pre-eclampsia or HELLP syndrome.

PURPOSE: Pregnancies of women with chronic kidney disease (CKD) are at higher risk of experiencing adverse perinatal (APO) and maternal outcome (AMO). Mean uterine artery pulsatility index (mUtA-PI) as well as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are helpful tools in diagnosing pre-eclampsia (PE) in women with CKD. The aim of the study was to evaluate the role of sFlt-1/PIGF ratio and mUtA-PI as predictors for APO, AMO, preterm delivery and decline of kidney function in CKD pregnancies. METHODS: A total of 28 CKD pregnancies with suspected PE/HELLP syndrome were retrospectively included, in whom both sFlt-1/PIGF and mUtA-PI were determined during the third trimester. APO was defined as fetal growth restriction, respiratory distress syndrome, intubation, admission to NICU, 5 min Apgar <7 and intracerebral hemorrhage. AMO was defined as the development of PE, HELLP syndrome or resistant hypertension. Decline of kidney function was defined as a 25% increase of creatinine level after delivery. RESULTS: Of all included women, eight (28.6%) developed a PE/HELLP syndrome. AMO (28.6%) and APO (32.1%) were frequently observed. ROC analyses revealed a predictive value for AMO and sFlt-1/PIGF or mUtA-PI. Neither sFlt-1/PIGF nor mUtA-PI could predict APO or decline of postnatal kidney function. mUtA-PI was a predictor for preterm delivery. CONCLUSION: Uterine Doppler and sFlt-1/PIGF are predictors of AMO in CKD pregnancies. Therefore, both markers might be helpful for an improved risk assessment. However, neither sFlt-1/PIGF nor mUtA-PI were able to predict a decline of postnatal kidney function or APO.