Additional value of advanced neurosonography and magnetic resonance imaging in fetuses at risk for brain damage.

OBJECTIVE: To assess the additional value of fetal multiplanar (axial, coronal and sagittal) neurosonography and magnetic resonance imaging (MRI) to that of the standard axial ultrasound planes in diagnosing brain damage in fetuses at high risk. METHODS: This was a prospective, multicenter, observational study. Women were eligible for participation if their fetus was at risk for acquired brain anomalies. Risk factors were congenital infection, alloimmune thrombocytopenia, fetal growth restriction, trauma during pregnancy, fetal hydrops, monochorionic twins and prior ultrasound finding suggestive of an acquired brain anomaly. Examinations of the fetal brain before birth comprised axial ultrasound and advanced neurosonography biweekly and MRI once. After birth, neonatal cranial ultrasound was performed at < 24 h and at term-equivalent age. Neonatal brain MRI was performed once at term-equivalent age. An expert panel blinded to medical information, including imaging findings by the other methods, evaluated the presence of periventricular echogenicity (PVE) changes, peri- and intraventricular hemorrhage (IVH) and changes in basal ganglia and/or thalami echogenicity (BGTE) on ultrasound, and the equivalent signal intensity (SI) changes on MRI. Conclusions on imaging findings were generated by consensus. The children were followed up with examinations for psychomotor development at 1 year of age, using the Touwen examination and Alberta Infant Motor Scale, and at 2 years of age using Bayley Scale of Infant Development-III (BSID-III) and behavioral, sensory profile and linguistic questionnaires; scores > 1 SD below the mean were considered suspicious for neurodevelopmental sequelae. RESULTS: Fifty-six fetuses were examined, and in 39/56 fetuses, all fetal-imaging modalities were available. PVE/SI changes were observed in 6/39, 21/39 and 2/39 fetuses on axial ultrasound planes, multiplanar neurosonography and MRI, respectively. IVH was found in 3/39, 11/39 and 1/39 fetuses, and BGTE/SI changes in 0/39, 12/39 and 0/39 fetuses, respectively. Outcome was suspicious for neurodevelopmental sequelae in 13/46 infants at 1 year, and at 2 years, 41/41 children had scores within 1 SD of the mean on BSID-III and 20 had scores > 1 SD below the mean on the behavioral (5/38), sensory profile (17/37) and/or linguistic (6/39) questionnaires. CONCLUSIONS: In this cohort of fetuses at risk for brain damage, the severity of acquired brain anomalies was limited. Nevertheless, multiplanar neurosonography detected more fetal PVE changes, IVH and/or BGTE changes compared to the standard axial ultrasound planes and MRI. Fetal MRI did not demonstrate any anomalies that were not seen on neurosonography. Neurodevelopmental outcome at 2 years of age showed no or mild impairment in most cases. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications.

A 35-year-old woman with recurrent severe placenta-mediated pregnancy complications in her 2 pregnancies asks: Will low-molecular-weight heparin help prevent recurrent placenta-mediated pregnancy complications in my next pregnancy? We performed a meta-analysis of randomized controlled trials (RCTs) comparing low-molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent placenta-mediated pregnancy complications. We identified six RCTs that included a total of 848 pregnant women with prior placenta-mediated pregnancy complications. The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for-gestational-age (SGA) newborn (<10th percentile), placental abruption, or pregnancy loss >20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; 95% CI, 0.32 to 0.86; P = .01; I(2), 69%, indicating moderate heterogeneity). We identified similar relative risk reductions with LMWH for individual outcomes, including any PE, severe PE, SGA <10th percentile, SGA <5th percentile, preterm delivery <37 weeks, and preterm delivery <34 weeks with minimal heterogeneity. LMWH may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required.

Eye-tracking visual patterns of sonographers with and without fetal motor assessment expertise.

OBJECTIVES: Fetal motor assessment (FMA) in addition to structural anomaly scan enhances prenatal detection of arthrogryposis multiplex congenita (AMC). In the Amsterdam UMC, sonographers are trained to perform FMA. We examined the effect of motor assessment training by comparing sonographers with (SMA) and without this training (S) on their qualitative motor assessment in fetuses with normal (FNM) and abnormal motility (FAM) and their visual processing by eye-tracking. METHODS: The study was performed from 2019 to 2020. Five SMA and five S observed five FNM and five FAM videos. Qualitative FMA consisted of six aspects of the general movement and the overall conclusion normal or abnormal. The visual processing aspects examined through eye-tracking were fixation duration, number of revisits per region of interest (ROI) and scanpaths of saccades between fixation points. RESULTS: Quality assessment by SMA revealed more correct aspects in FNM than in FAM but overall conclusions were equally correct (92-96 %). S scored aspects of FNM better than in FAM, but overall conclusion correct only in half of FNM and three quarters of FAM. Eye-tracking of SMA and S showed fixation duration and revisits with similar distributions per ROIs for FNM and FAM, but SMA perform more trunk revisits in FNM. Scanpaths had smaller circumference, less outliers and more consistency in SMA than S. CONCLUSION: This modest population of qualified sonographers showed that additional FMA training improved qualitative motor assessment. Eye-tracking revealed differences in visual processing and stimulates continuous education for professionals active in the detection of these rare diseases.

Cardiovascular risk after hypertensive disorders of pregnancy in women with and without inheritable Thrombophilia.

Aim of this study was to compare cardiovascular risk in women with and without inheritable thrombophilia after hypertensive disorders of pregnancy (HDP). Blood pressure, anthropometrics and blood samples were measured 9-13 years after early-onset (<34 weeks) HDP. Amongst the 114 women included, no differences in hypertension (31.1% vs. 33.7%, OR 0.90 95% CI (0.29-2.79)), body mass index > 25 kg/m2 (43.8% vs. 53.1%, OR 0.69 95% CI (0.24-2.00)) or metabolic syndrome (18.8% vs. 13.3%, OR 1.51 95% CI (0.38-6.02)) were found. These data show similar cardiovascular risk profile in women with and without inheritable thrombophilia.

Uterine rupture in The Netherlands: a nationwide population-based cohort study.

OBJECTIVE: To assess incidence of uterine rupture in scarred and unscarred uteri and its maternal and fetal complications in a nationwide design. DESIGN: Population-based cohort study. SETTING: All 98 maternity units in The Netherlands. POPULATION: All women delivering in The Netherlands between August 2004 and August 2006 (n = 371,021). METHODS: Women with uterine rupture were prospectively collected using a web-based notification system. Data from all pregnant women in The Netherlands during the study period were obtained from Dutch population-based registers. Results were stratified by uterine scar. MAIN OUTCOME MEASURES: Population-based incidences, severe maternal and neonatal morbidity and mortality, relative and absolute risk estimates. RESULTS: There were 210 cases of uterine rupture (5.9 per 10,000 pregnancies). Of these women, 183 (87.1%) had a uterine scar, incidences being 5.1 and 0.8 per 10,000 in women with and without uterine scar. No maternal deaths and 18 cases of perinatal death (8.7%) occurred. The overall absolute risk of uterine rupture was 1 in 1709. In univariate analysis, women with a prior caesarean, epidural anaesthesia, induction of labour (irrespective of agents used), pre- or post-term pregnancy, overweight, non-Western ethnic background and advanced age had an elevated risk of uterine rupture. The overall relative risk of induction of labour was 3.6 (95% confidence interval 2.7-4.8). CONCLUSION: The population-based incidence of uterine rupture in The Netherlands is comparable with other Western countries. Although much attention is paid to scar rupture associated with uterotonic agents, 13% of ruptures occurred in unscarred uteri and 72% occurred during spontaneous labour.

One-year infant outcome in women with early-onset hypertensive disorders of pregnancy.

OBJECTIVES: To evaluate the role of plasma volume expansion on 1-year infant outcome after severe hypertensive disorders of pregnancy and to determine prognostic factors for adverse neurodevelopmental infant outcome. DESIGN: Randomised controlled trial, observational prognostic study. SETTING: Two university hospitals in Amsterdam, The Netherlands. POPULATION: One hundred and seventy-two infants alive of 216 mothers with severe hypertensive disorders of pregnancy who were randomised for a temporising management strategy with or without plasma volume expansion. METHODS: At 1 year of corrected age, a neurological examination according to Bayley (mental development index [MDI] and psychomotor development index [PDI]) and Touwen was performed. MAIN OUTCOME MEASURES: Adverse neurodevelopmental infant outcome was defined as a MDI/PDI score below 70 and/or an abnormal Touwen. Risk factors for adverse neurodevelopmental outcome were explored by univariate and multivariate analyses. RESULTS: Adverse neurodevelopmental infant outcome was observed in 31 infants (18%). There were no differences between the randomisation groups. In multivariate analysis, an association with abnormal umbilical artery/middle cerebral artery Doppler ratio higher than the median, major neonatal morbidity, higher education of the parents, multiparity and Caucasian ethnicity was observed. CONCLUSION: Nearly 70% of the infants were alive at 1 year without adverse neurodevelopmental outcome. Maternal plasma volume expansion during pregnancy has no effect on 1-year infant outcome. The prediction of adverse outcome at 1 year by perinatal parameters is limited.

Severe maternal morbidity during pregnancy, delivery and puerperium in the Netherlands: a nationwide population-based study of 371,000 pregnancies.

OBJECTIVE: To assess incidence, case fatality rate, risk factors and substandard care in severe maternal morbidity in the Netherlands. DESIGN: Prospective population-based cohort study. SETTING: All 98 maternity units in the Netherlands. POPULATION: All pregnant women in the Netherlands. METHODS: Cases of severe maternal morbidity were collected during a 2-year period. All pregnant women in the Netherlands in the same period acted as reference cohort (n = 371,021). As immigrant women are disproportionately represented in Dutch maternal mortality statistics, special attention was paid to the ethnic background. In a subset of 2.5% of women, substandard care was assessed through clinical audit. MAIN OUTCOME MEASURES: Incidence, case fatality rates, possible risk factors and substandard care. RESULTS: Severe maternal morbidity was reported in 2552 women, giving an overall incidence of 7.1 per 1000 deliveries. Intensive care unit admission was reported in 847 women (incidence 2.4 per 1000), uterine rupture in 218 women (incidence 6.1/10,000), eclampsia in 222 women (incidence 6.2/10,000) and major obstetric haemorrhage in 1606 women (incidence 4.5 per 1000). Non-Western immigrant women had a 1.3-fold increased risk of severe maternal morbidity (95% CI 1.2-1.5) when compared with Western women. Overall case fatality rate was 1 in 53. Substandard care was found in 39 of a subset of 63 women (62%) through clinical audit. CONCLUSIONS: Severe maternal morbidity complicates at least 0.71% of all pregnancies in the Netherlands, immigrant women experiencing an increased risk. Since substandard care was found in the majority of assessed cases, reduction of severe maternal morbidity seems a mandatory challenge.

General movements in infants born from mothers with early-onset hypertensive disorders of pregnancy in relation to one year's neurodevelopmental outcome.

BACKGROUND: Assessment of general movements (GMs) at three months is considered useful for prediction of adverse neurological outcome in high risk infants. AIMS: To study the prevalence of abnormal GMs in infants born from women with early-onset hypertensive disorders of pregnancy and the association of GMs with neurodevelopmental outcome at one year. STUDY DESIGN: Prospective study, part of a randomised controlled trial of pre-birth management strategies. SUBJECTS: Infants born from women with early-onset hypertensive disorders of pregnancy. OUTCOME MEASURES: GMs observation and neurological examination at term and three months corrected age; at one year neurological examination and Bayley Scales of Infant Development. RESULTS: From 216 women included, 175 of 178 surviving infants (mean gestational age 31.6 weeks [SD 2.3], mean birth weight 1346 grams [SD 458]), were examined at three months. At term age normal, mildly abnormal and definitely abnormal GMs were observed in 54%, 36% and 10% respectively; and at three months in 47%, 40% and 13%. Mildly or definitely abnormal GMs at three months were not associated with abnormal neurological examination at one year, however, they were associated with delayed psychomotor development at one year (p = 0.01). CONCLUSIONS: In this prospective study, including small for gestational age, preterm infants about half of them did not have normal GMs at term and three months. There was no association of GMs at term nor three months with neurological outcome at one year, but there was a significant association of GMs at three months with one year psychomotor development.

Neurobehavioural outcome in 6-18 year old children after trauma in pregnancy: Case-control study.

BACKGROUND: Maternal trauma complicates pregnancy in approximately 7%. Long-term development of children exposed to maternal trauma is unknown. AIM: To determine neurobehavioural outcome of children (6-18 years) born after maternal trauma in pregnancy compared to a matched control group. STUDY DESIGN: Case-control study performed at a tertiary medical centre. SUBJECTS: All consecutive children born after maternal hospitalization for trauma during pregnancy between 1995 and 2005. Controls were children born at the same hospital and period after an uneventful pregnancy. OUTCOME MEASURES: Trauma type and severity (Injury Severity Score, ≥9: severe); information from medical files at admission (cases). All mothers filled out two questionnaires about the infant; 1. concerning health, motor development and educational level, 2. concerning behavioural development through the validated Dutch version of the Child Behavior Checklist (CBCL). RESULTS: Questionnaires were returned by 34 cases and 28 controls. The traumas concerned mainly motor vehicle accidents and falls, and 3/34 had severe injuries. No differences in health, motor development, educational level and CBCL was found between the cases and controls, except for more hospitalization in the cases (p = 0.009). CONCLUSION: Long-term follow-up of a limited population of children 6-18 years after exposure of mainly non-severe trauma before birth is similar to a control population except for unexplained more hospitalization in the cases.

Trauma in pregnancy, obstetrical outcome in a tertiary centre in the Netherlands.

PURPOSE: To determine obstetrical outcome and predictive value of obstetrical symptoms and diagnostic examinations on adverse outcome after maternal trauma in pregnancy. MATERIALS AND METHODS: Retrospective study in a Dutch tertiary medical center, including women admitted for trauma in pregnancy between 1995 and 2005 and infants born from these pregnancies. Characteristics at trauma (type of trauma, severity) and obstetrical outcome were recorded, as well as prevalence and severity of trauma; prevalence of obstetrical symptoms and abnormal diagnostic examinations. Composite adverse obstetrical outcome was defined as fetal death, placental abruption, birth <37 weeks and/or birth weight <10th percentile. The predictive value of obstetrical symptoms or abnormal diagnostic tests on an adverse pregnancy outcome was analyzed (logistic regression analysis). RESULTS: Trauma admissions occurred in 10 per 1000 deliveries. Injuries were non-severe in 147/159 (92%). Obstetrical symptoms and/or abnormal diagnostic tests were present in 64/159 (40%) and 12/159 (8%) respectively. Adverse pregnancy outcome was encountered in 17/80 cases, mainly preterm births (13/80 (16%)). Severe injuries were predictive for an adverse pregnancy outcome. CONCLUSIONS: We found a considerable rate of trauma during pregnancy. There was an increased risk for preterm birth and severity of injuries was predictive for adverse outcome.

Dynamics and incidence patterns of maternal complications in early-onset hypertension of pregnancy.

OBJECTIVE: To describe the variable disease expression and the patterns of development of major maternal morbidity and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome in women with different subtypes of hypertensive disorders of pregnancy. DESIGN: Prospective cohort study. SETTING: Two university hospitals, tertiary care centres. POPULATION: Two hundred and sixteen women participating in a randomised trial of temporising management in early-onset hypertensive disease (PETRA trial). Women were between 24 and 34 completed weeks and had either HELLP syndrome, severe pre-eclampsia, eclampsia or hypertension and fetal growth restriction. Women were delivered in the event of fetal marked heart rate abnormalities, pulmonary oedema, therapy-resistant hypertension or recurrent HELLP syndrome. METHODS: Trial data were reanalysed to assess the time of onset of major maternal morbidity (e.g. pulmonary oedema, liver haematoma), HELLP syndrome and clinical disease. Associations between clinical parameters and prolongation of pregnancy were explored using logistic regression. MAIN OUTCOME MEASURES: Diagnosis from admittance to discharge, major maternal morbidity and prolongation of pregnancy. RESULTS: The median time to delivery or fetal death was 8.2 (range 0.1-44) days. At study entry, 56 women (26%) had more than one diagnosis; this increased to 171 women (79%) by the time of discharge. The incidence of major maternal morbidity (total 26) was 4.2% at 2-4 days after inclusion and a mean of 1.7% (range 0-2%) thereafter per time frame of 3 days. The mean incidence of new or recurrent HELLP syndrome episodes was 5.5% (range 1.9-8.7%) per time frame of 3 days during the first 3 weeks after inclusion. CONCLUSIONS: Pre-eclampsia is a dynamic disease, with extensive overlap of subtypes of the syndrome. Prolongation of pregnancy in early-onset hypertensive disorders results in the development of further HELLP syndrome episodes and reversible major maternal morbidity but may improve perinatal healthy survival.

Haemodynamic changes in the second half of pregnancy: a longitudinal, noninvasive study with thoracic electrical bioimpedance.

OBJECTIVE: Maternal cardiovascular adaptations to pregnancy are necessary for an adequate fetomaternal circulation. However, the time course of physiological haemodynamic changes during the second half of pregnancy remains unclear. Various methods, invasive and noninvasive, are described to measure these changes. The thoracic electrical bioimpedance (TEB) technique is a method which is especially suitable to measure haemodynamic changes over time. The aim of the study was to determine both individual and group trends of haemodynamic changes in healthy pregnant women during the second half of pregnancy by means of TEB. Outcome variables are heart rate (HR), stroke volume (SV), cardiac output (CO) and blood pressure. DESIGN: Longitudinal study. SETTING: Outpatient antenatal care clinic of university hospital. POPULATION: A total of 22 healthy nonsmoking women with an uncomplicated singleton pregnancy and without pre-existing vascular disorders were invited. METHODS: TEB and blood pressure measurements were performed at each regular visit from about 24 weeks of gestation through term age. MAIN OUTCOME MEASURES: Trends were calculated with the random effects model. RESULTS: Data obtained from 19 women were analysed, with a median of eight (range 3-11) measurements. HR showed a linear increase (P < 0.0005) and a quadratic trend (P < 0.0005). SV decreased linearly (P = 0.046), without a quadratic course. CO remained stable over time. CONCLUSION: During the second half of physiological pregnancy, significant trends could be determined. An increase in HR, a decrease in SV, a stable CO and an increase in systolic and diastolic blood pressures were found.

Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?

OBJECTIVES: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome. METHODS: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies. RESULTS: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups. CONCLUSIONS: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment.

[Intra-uterine death caused by fetal akinesia]. / Intra-uteriene sterfte door foetale bewegingsarmoede: het belang van diagnostiek na een vruchtdood.

BACKGROUND: When two successive pregnancies end in intra-uterine fetal death (IUFD), the question of whether it is coincidental or if there is an underlying abnormality arises. Although diagnostic investigations into the underlying cause are not always carried out after IUFD, they are recommended by the professional body. CASE DESCRIPTION: A 28-year-old female attended our gynaecology outpatient clinic for a second opinion following two intra-uterine fetal deaths. Her own treating physician was of the opinion that there was no connection between the two IUFDs. After a multidisciplinary evaluation, the phenotype fetal akinesia deformation sequence (FADS) was diagnosed in both cases. This is a rare, clinically and aetiologically heterogeneous group of disorders. Thereafter the patient and her husband were offered specific pre-conception counseling. CONCLUSION: Every IUFD justifies systemic and multidisciplinary investigation to determine any underlying aetiology such as FADS. This may contribute to better pre-conception advice and prenatal individualised diagnostics in a subsequent pregnancy.

Echogenicity changes in the fetal brain, a 6-year follow-up study.

OBJECTIVE: To asses the relation between echogenicity changes in the fetal brain and neurodevelopmental outcome until 6 years of age. METHODS: Fetuses (n = 124) from pregnancies affected by hypertensive disorders (n = 64) or preterm labor (n = 60) at risk for preterm birth (26-34 weeks gestation) were studied. Moderate echogenicity changes (periventricular grade IB, II; intraventricular grade II-III; local basal ganglia/thalami) in the fetal and neonatal brain were related to neurological outcome and Griffiths mental developmental scales quotients at 1, 2 and 6 years. Multiple regression analysis tested the influence of moderate echogenicity changes and perinatal clinical characteristics on composite outcome (death or abnormal neurodevelopment). RESULTS: Moderate echogenicity changes were present in 37/124 (30%) fetuses. Median gestational age and weight at birth were respectively 31 weeks (range 26-43), 1314 g (range 550-4330), mortality was 19%, follow-up loss 10%. Composite outcome was abnormal in 47/124 (38%). Fetal and neonatal moderate intraventricular echodensities were related to cerebral palsy at 6 years (p < 0.04). In the multiple regression analysis only gestational age was related to composite outcome (p = 0.005). CONCLUSIONS: Moderate intraventricular echodensities in the fetal brain related to cerebral palsy at 6 years of age. Gestational age at birth was the main predictor of abnormal composite outcome.