Calf circumferences in fetuses and neonates with and without talipes equinovares. A prospective cohort study.

OBJECTIVE: Children and adults with talipes equinovarus (TEV) have smaller calves and shorter feet compared to non-affected controls. Do these changes have a prenatal onset? METHODS: A prospective cohort study (January 2020-July 2021) was conducted with serial ultrasonographic measurements at 20 and 28 weeks gestation and measurements directly and 6 weeks after birth. Calf circumference and width, foot length and length of humerus, ulna, radius, femur, tibia and fibula were measured in TEV and were compared to a control population. Calculated sample size necessitated a minimal population of 10 cases with TEV and 50 controls. RESULTS: Twenty cases with TEV and 62 controls were included. Fetal calf circumference (p < 0.001) and width (p < 0.001) were smaller in the TEV group in comparison to the control group, which persisted after birth. Growth in foot length (p < 0.001) and calf width (p 0.003) declined prenatally over time. The bone lengths and upper leg circumference were not smaller or shorter in TEV compared to controls. CONCLUSION: This prospective cohort study demonstrated the prenatal onset of reduced calf and foot size in fetuses with TEV from 20 weeks and onwards, which persists directly after birth. To investigate whether reduction in circumference initiates TEV or is caused by TEV, further examination is needed.

Care Pathway for Foetal Joint Contractures, Foetal Akinesia Deformation Sequence, and Arthrogryposis Multiplex Congenita.

INTRODUCTION: The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS). METHODS: The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form. RESULTS: An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies. DISCUSSION/CONCLUSION: The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.

Fetal akinesia deformation sequence and massive perivillous fibrin deposition resulting in fetal death in six fetuses from one consanguineous couple, including literature review.

BACKGROUND: Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD. METHODS: Fetal ultrasound examination, motor assessment, genetic testing, postmortem examination, and placenta histology are presented (2009-2019). Literature was reviewed for the association between congenital anomalies and MPFD. RESULTS: All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. From 63/1999 manuscripts, 403 fetal outcomes were mobilized. In 14/403 fetuses, congenital abnormalities in association with MPFD were seen of which two fetuses with contractures/FADS facial anomalies. CONCLUSION: The low prevalence of fetal contractures/FADS facial anomalies in association with MPFD in the literature review supports the possible fetal or genetic contribution causing FADS and MPFD in our family. This study with literature review supports the finding that fetal, fetoplacental, and/or genetic components may play a role in causing a part of MPFDs.

Fetal akinesia deformation sequence, arthrogryposis multiplex congenita, and bilateral clubfeet: Is motor assessment of additional value for in utero diagnosis? A 10-year cohort study.

OBJECTIVE: The diagnosis of fetal akinesia deformation sequence (FADS) is a challenge. Motor assessment is of additional value to advanced ultrasound examinations (AUE) for in utero FADS diagnosis before 24 weeks of gestation. METHODS: All consecutive fetuses with greater than or equal to two contractures on the 20 week structural anomaly scan (2007-2016) were included. Findings at AUE, including motor assessment were analysed and related to outcome. RESULTS: Sixty-six fetuses fulfilled the inclusion criteria. On the basis of the first AUE, FADS was suspected in 13 of 66, arthrogryposis multiplex congenita (AMC) in 12 of 66, bilateral pes equinovares (BPEV) in 40 of 66, and Holt-Oram syndrome in one of 66. On the basis of the first motor assessment, the suspected diagnosis changed in 19 of 66, in 13 of 66 worsening to FADS, six of 66 amelioration from FADS, and confirmed FADS in seven of 13. The result was 20 FADS, seven AMC, and 38 BPEV. Second AUE in 44 fetuses showed additional contractures in two of eight FADS, and one intrauterine fetal death (IUFD). The second motor assessment changed the diagnosis in three of 43, one worsening from BPEV into FADS, two ameliorations from FADS, and confirmed FADS in seven by deterioration of motility. The result was nine FADS, six AMC, and 29 BPEV. CONCLUSION: The results suggest that motor assessment has additional value to distinguish between FADS, AMC, and BPEV.

Fetal MRI, lower acceptance by women in research vs. clinical setting.

AIM: To determine acceptance of pregnant women to undergo fetal magnetic resonance imaging (MRI) examination in research and clinical setting. METHODS: A prospective study included a research group [part of a study comparing brain ultrasound (US) to MRI in fetuses at risk for acquired brain damage] and a clinical group [fetuses with suspected (brain) anomalies after structural US examination] from 2011 to 2014. All women were advised to use sedatives. MRI declinations, use of sedation, MRI duration and imaging quality were compared between both groups. RESULTS: Study participation was accepted in 57/104 (55%) research cases. Fetal MRI was performed in 34/104 (33%) research and 43/44 (98%) clinical cases. Reasons to decline study participation were MRI related in 41%, and participation was too burdensome in 46%. Acceptance was highest for indication infection and lowest in alloimmune thrombocytopenia and monochorionic twin pregnancy. Sedatives were used in 14/34 research and 43/43 clinical cases. Scan duration and quality were comparable (21 and 20 min in research and clinical cases, respectively, moderate/good quality in both groups). CONCLUSIONS: Pregnant women consider MRI more burdensome than professionals realize. Two-third of women at risk for fetal brain damage decline MRI examination. Future studies should evaluate which information about fetal MRI is supportive.

Congenital Cytomegalovirus Infection in the Absence of Maternal Cytomegalovirus-IgM Antibodies.

BACKGROUND: Congenital cytomegalovirus (cCMV) infections are the most prevalent intrauterine infections worldwide and are the result of maternal primary or non-primary infections. Early maternal primary infections are thought to carry the highest risk of fetal developmental abnormalities as seen by ultrasound; however, non-primary infections may prove equally detrimental. METHODS/RESULTS: This case series presents 5 cases with fetal abnormalities detected in the second and third trimester, in which cCMV infection was ruled out due to negative maternal CMV-IgM. DISCUSSION: This series highlights the possible pitfalls in serology interpretation and fetal diagnosis necessary for appropriate parental counseling. Once fetal abnormalities have been confirmed and cCMV is suspected, maternal CMV serostatus and fetal infection should be determined. Maternal CMV serology may be ambiguous; therefore, caution should be exercised when interpreting the results.

Effect of (minor or major) maternal trauma on fetal motility: A prospective study.

BACKGROUND: Fetal motility represents the spontaneous activity of the central nervous system and as such can be used to evaluate its functional integrity. Maternal mechanical trauma in pregnancy is a risk factor for hypoxic ischemic brain injury and can potentially affect the CNS and fetal motility. AIM: To study motility in fetuses after maternal trauma. STUDY DESIGN: Prospective study; 1-h sonographic observations at 2-8h (T1), 24-72h (T2) and >72h (T3) after trauma. SUBJECTS: Fetuses exposed to trauma after 20weeks gestational age. OUTCOME MEASURES: Motor aspects; differentiation into specific movement patterns, quality and quantity of general movements were compared to a normal population. Obstetrical outcome; neurological outcome at term and 1year of age. RESULTS: Sixteen fetuses were examined between 2012 and 2014. Median gestational age at time of trauma was 25+6 (range 20-38) weeks. Most traumas were traffic accidents or falls, injuries were mainly minor. Motility assessment showed abnormal differentiation in 2/16; 2/14 and 0/16; abnormal quality in 2/16; 3/14 and 6/16; and abnormal quantity in 6/16, 9/14 and 9/16 at T1, T2 and T3 respectively. Preterm delivery occurred once. Neurological development was normal in 13/14 infants at term and 14/14 at one year. CONCLUSIONS: This study shows that maternal trauma affected fetal motility in the majority of the fetuses. The changes in motility support the concern that even minor mechanical trauma may have influence on the functional integrity of the central nervous system, although no neurological sequelae were present at 1year.

Placental retention in late first and second trimester pregnancy termination using misoprostol: a retrospective analysis.

OBJECTIVE: Termination of pregnancy (TOP) for medical reasons is regularly performed using misoprostol. Presence of placental remnants followed by curettage, frequently complicate the procedure. Aim of this analysis is to audit our current policy for medical termination in late first and second trimester, looking at the management of third stage. METHODS: A retrospective analysis of patient data was performed. Included were patients that underwent medical TOP in late first or second trimester. Patients were reviewed 6 weeks postdelivery. Characteristics of procedure, patient and pregnancy were analysed to determine factors associated with an increased risk of retained placenta/placental remnants. RESULTS: We included 175 patients. Eighty-five patients (48%) underwent curettage immediately after delivery because of retained placenta or because placental remnants were suspected. Nineteen patients (11%) underwent curettage at later stage. All tissue was examined microscopically for confirmation of placental tissue. Analysis of characteristics of procedure, patients and pregnancies did not identify factors associated with an increased risk of retained placenta or placental remnants. CONCLUSION: A large number of immediate and late curettages was seen after medical TOP. Misoprostol-dose might play a role and the role of ultrasonographic assessment of the uterine cavity immediately post-placenta-delivery needs to be studied.