This review of the literature adds significantly to our knowledge of how comprehensive is the influence of congenital anomalies on fetal motility. Hyper- and hypokinetic changes in motor aspects in relation to normal motor development were found to be associated with congenital anomalies. The anomalies inducing hypokinetic motility consisted mainly of autosomal recessive disorders with neuromuscular–skeletal–skin disorders and those inducing hyperkinetic disorders consisted mainly of sporadic or low-recurrence-rate structural or chromosomal disorders with CNS involvement. The majority had an adverse outcome (14% alive with a handicap varying according to the underlying anomaly). With respect to the assessment procedure, the following changes in motor development were determined. First, the differentiation into SMPs was reduced in both cases of congenital abnormalities with hypokinetic movements and in those with hyperkinetic movements (FAHS and anencephaly). Second, qualitative changes were investigated in 62% of cases. Third, a quantitative change of movement, either increased or decreased, was investigated in 76% of cases. The normal distribution of increase and decrease in ongoing activity during one burst of general movements can disappear in fetuses with congenital abnormalities. Abnormal temporal patterning was found in fetuses with hyperkinetic movements: a burst–pause pattern in activity was observed in those with anencephaly, Fanconi anemia and myoclonic encephalopathy; continuous activity was observed in fetuses with chromosomal anomalies (trisomy 18, trisomy 1q and trisomy 5p). Posture was affected in 42% of cases and this was not limited to fetuses with hypokinetic movements.
Over the years, a stable number of publications has appeared relating to congenitally abnormal fetuses with sonographic identification of motor and or postural abnormalities. From their assessment procedures it was evident that most of the investigators put considerable effort into using adequate observation times in the set-up of their studies; most examinations lasted > 15 min. Adequate duration of observation is gestational-age-related; 15 min can be considered sufficient in observations of fetuses aged < 20 weeks' gestation, 30 min is required between 20 and 30 weeks and ≥ 60 min thereafter4. There was a difference in the assessment procedures performed between the group of fetuses with hypokinetic and the group with hyperkinetic motility. The hypokinetic group was quantified more frequently than it was qualified (85% and 45%, respectively), while the reverse was true for the hyperkinetic group (64% and 84%, respectively). It is important to realize that a larger proportion of the quantified hypokinetic group, compared with the hyperkinetic group, had unknown observation periods, while important conclusions such as reduced activity or akinesia are presented in these articles. On the other hand, these hypokinetic fetuses were examined more often than were hyperkinetic ones for the emergence of abnormal movements. This interest in the emergence of abnormal movements fits with the effort to offer prenatal diagnostic possibilities in the absence of invasive diagnostics or conclusive diagnosis by sonographically visualized structural abnormalities in this diverse group of neuromuscular–skeletal–skin disorders with varying onset of motor and postural anomalies.
A number of critiscisms of the various published studies must be made at this point, because the reproducibility of the assessment procedure was influenced negatively by several aspects of the research, which hampered comparison between investigations. First, although SMPs were applied in the majority of motor examinations, their differentiation was only studied for a limited number of congenital abnormalities, despite the fact that their early and strongly age-related differentiation allows investigation as early as the first trimester. The attention to general movement, the most frequently occurring SMP, was also limited, despite its higher reproducibility compared with the NSMPs. Moreover, in addition to the higher reproducibility, judgement of the quality of general movements has proved to be of prognostic value for the integrity of the nervous system and later neurological outcome in congenitally normal but growth-restricted fetuses9, 10.
Second, qualitative changes were described in various inexact ways, using such adjectives as ‘feeble’, ‘vigorous’, ‘jerky’ and ‘abrupt’. In cases of congenital abnormalities, the movement repertoire is often damaged to such an extent that systematic comparison of the different qualitative aspects with cases of normal motility can help to elucidate how differently the various SMPs, including general movement, are performed in abnormal cases. Observing abnormal motility demonstrates impressively how much of the normal variation in amplitude, speed, participating body parts, fluency, and increasing and decreasing activity is lacking. Reporting these aspects more precisely creates the baseline characteristics of the quality of motility and therefore enhances reproducibility.
Third, though quantitative changes have been examined extensively, definitions of single movements or their duration vary greatly. It has been determined that the best interval between bursts of normal motor activity is 1–3 s in order to allow discrimination between short-lasting and long-lasting activity bursts (in general movements or body movements)61. Despite the fact that it is widely accepted that a characteristic of normal motility is the wide range in activity, most effort has still been placed on simple assessment of quantity. There is a growing awareness that quantitative assessment seems to be of more value for demonstrating trends in the wide variance of activity than for locating individual fetuses at high risk. In 34% of the studies reviewed, the duration of movements was not even presented, making quantification a non-reproducible result. Only extremes in abnormal quantity will be helpful to determine if an activity is not within the normal range, for example, continuous activity or absence of or severe reduction in motility over a well-defined observation period. Temporal patterning has only been studied in a limited way, and the organization of behavioral states, as one of the most important milestones in temporal patterning, was studied only twice.
Finally, though population characteristics were, for the most part, defined thoroughly in the studies reviewed, they are not presented in this overview because most publications were case histories, with a few exceptions reporting the same assessment procedures in a number of fetuses with the same congenital abnormalities, thus enhancing the reproducibility of the assessment44, 50, 51, 60. There is also a realistic possibility of bias in the presented articles on congenital abnormalities, if only cases in which the abnormal findings of motor anomalies were found to be associated with congenital abnormalities were submitted for publication.
Despite the limitations of the studies described here, the following milestones in neuromuscular development could be determined.
Differentiation into SMPs was found to be reduced from the onset of the disorder, regardless of in which of the three trimesters this occurred. The start and subsequent differentiation of the movement patterns during the first trimester appeared to be based on a minimal neural and myogenetic structure62. However, the development of the neuromuscular system must be sufficient to facilitate spontaneous motility from about 7 weeks' gestation onwards, and the emergence of all the different SMPs, in the 7 weeks thereafter, which remain recognizable throughout gestation. The heterogeneous etiology of FAHS may start its destructive effects on various systems at different gestational ages, and there must be variable expression since the offspring of one family showed variance of a few weeks in the onset of the disease14, 37. This has also been illustrated in a series of proven central core disease myopathies (histologically and by mutations in the ryanodine receptor gene)39. This disease is considered as a relatively benign, non-progressive hypotonia during early childhood. However, it can also have severe forms, with fetal akinesia and postural anomalies, like the one of 36 fetuses with FAHS in this overview reported to be alive. This fetus needed ventilatory assistance during the 1st month, had swallowing difficulties for 5 months and received intensive orthopedic care thereafter.
In contrast to FAHS, with its onset of abnormal motor activity at various ages, the quality of general movement in anencephalics was found to be influenced from its very emergence, as found in a case at 10 weeks59, explained by the reduced supraspinal influences to induce variance and thus complexity of the movement. Likewise, the reduced differentiation in SMPs occurs in anencephalics from the very beginning of motor activity, and has been demonstrated throughout the period between 10 and 35 gestational weeks60. It is impressive that even with histologically proven absence of cervical cord, isolated arm movements can be observed, suggesting that in the absence of supraspinal connections, parts of the body can move using merely ectopic motoneurons either inside or outside the CNS60. The mechanisms of disintegration of the nervous system can result in various motor abnormalities within a certain disorder. This is clearly demonstrated within the reported anencephalic, FAHS and restrictive dermopathy fetuses, all of which have extensive but variable motor anomalies. In the latter two disorders, a worsening of quality with age was observed. As mentioned earlier, it is important to realize that the underlying cause of FAHS varies and often is not even known. Despite the seriousness of the disorder, it does not always occur in both upper and lower extremities, necessitating very careful follow-up in cases in which only one extremity deformity is found before 24 weeks. This is in contrast to older fetuses or neonates, in which the finding of asymmetrical postural anomalies is considered reassuring. The important overview of Smith's Recognizable Patterns of Human Malformation63 describes underlying disorders of asymmetrical posture deformities as being likely caused by extrinsic factors for intrauterine constraint (e.g. uterine malformation), whereas symmetrical deformities are caused by intrinsic factors (e.g. CNS, peripheral nervous system, muscle, connective tissue, skeleton). Another expression of the varying involvement of motor activity is reflected in the fact that the quality of movements may not undergo the expected reduction in amplitude and speed: short-lasting high-speed bursts of activity (abruptness) have also been encountered in the case of FAHS. While it seems logical that, in cases of restrictive dermopathy, the skin restriction limits the amplitude and speed of movements, abruptly performed general movements were also seen in one fetus31. These abrupt movements must be explained by a problem that is initiated more centrally. This is also the case for leg movements in spina bifida aperta, which can vary from normal to abnormal hypokinetic to hyperkinetic, depending on the supraspinal connections44.
In this review, 16 different congenital disorders inducing mostly hypokinetic motility and 17 inducing mostly hyperkinetic motility have been reported. In comparison to our extensive knowledge for neonates (for example, Smith's Recognizable Patterns in Human Malformation63 reported 52 disorders with frequent hypotonicity and 35 with frequent hypertonicity or seizures), this is just the beginning. When comparing fetal and neonatal data it is important to realize that while findings before birth are confirmed, they may also undergo further development. This is the case, for example, for two anomalies with hypokinetic movements before birth (Smith-Lemli–Opitz and Prader–Willi syndrome). These neonates remain hypokinetic, but can have seizures thereafter as well. The six cases with abnormal quality of motor activity in the chromosomal anomaly, trisomy 21, are in agreement with the findings of Mazzone et al.64 on general movements in children with Down syndrome, who also demonstrated heterogeneity among the children. As such, we do not advocate any application for clinical practice, but point out that even in trisomy 21, qualitative motor changes can be detected.
Quantitative changes in motor activity in the fetuses described was often found to be influenced in such a way that the normal waxing and waning of an ongoing general movement instead became reduced, continuous or burst–pause activity. These phenomena are not transient. Reduced motility is found especially in anomalies with limitations caused by central and peripheral nervous system abnormalities as well as muscular involvement, whereas increased, continuous and burst–pause activity is found particularly when there are abnormalities in the CNS hindering normal patterning.
Behavioral states develop late in pregnancy (36 weeks) and are considered to be an expression of the integrity of the nervous system. They have been found to be one of the first parameters of fetal well-being that are influenced in cases of FGR caused by uteroplacental insufficiency65, 66. In the severe congenital disorders presented here, their late emergence means that they are of limited diagnostic value. In the case of Prader–Willi syndrome, prolonged inactive periods were described19, and this has been confirmed by others. These prolonged inactive periods with short active periods correspond with the diminished quantity of the fetal movements.
The normal development of joints starts at about 5.5 weeks' gestation. By 7 weeks, many joint spaces exist and movement is possible from 8 weeks onwards. Movement is thought to be essential for the normal development of the joints62. There is a growing awareness of the influence of limitation of movement on posture even under physiological circumstances. Fetuses in cephalic presentation are more likely to have flexed wrists than are fetuses in breech presentation. The wrist of the cephalic fetus is situated in the lower segment, whereas the breech fetus has more room in the fundus of the uterus67 (since both have a preferred elbow flexion, the environmental influence further away from the lower segment and fundus has been shown to be identical).
Contractures are secondary to intrinsic (neuromuscular, skeletal, skin) or extrinsic (fetal crowding and constraint) factors. Intrinsic factors often lead to symmetrical contractures, and extrinsic ones generally to asymmetrical contractures63. Neonates born with arthrogryposis can be divided into three main categories: those with limb involvement only; those with involvement of the trunk, craniofacies or viscera, and limbs; those with severe CNS dysfunction68. An extensive differential diagnosis is provided in this article. In general, the outcome of the first group is good, as is that of the second, depending on the specific diagnosis, while the third group has a poor outcome, with about 50% dying within the 1st year.
Sonographic motor assessment is not implemented routinely in the care of high-risk pregnancies. As obstetricians we wish to be able to distinguish the fetus at risk for developing a motor handicap after birth, for example in the case of FGR, or the fetus at risk of miscarriage because of a congenital abnormality involving the CNS. Better insight into the continuity of movements before and after birth would enhance the possibility of the clinical application of sonographic motor assessment and would make necessary collaboration with pediatricians active in this field. Longitudinal studies on small groups of fetuses at high risk for congenital abnormalities are worthwhile and need to be extended to larger groups for testing the reliability of its application.
Because not all anomalies can be detected by ultrasound, magnetic resonance imaging or chromosomal, DNA or metabolic testing, previous investigators have shown their efforts in the clinical application of motor assessment by publishing case histories. However, these researchers have not systematically studied motor assessment. Most studies were case reports with no longitudinal approach to investigate changes over time or after birth; both are necessary for testing the reliability of fetal motor assessment in these rarely occurring disorders with respect to later neuromuscular outcome. As demonstrated in FAHS, the first sign can be limited to one extremity contracture only. Thus, a repeat examination after 2 weeks would indicate if there has been progressive worsening of a centrally located rather than merely a peripheral disorder.
In 44% of cases the motor anomalies of the various congenital abnormalities were found after 24 weeks' gestation, an important age in daily practice taking into consideration the possibilities of viability and termination of pregnancy. Ranking the prevalence of these SMPs per observation period might be helpful because ranking is found to be a rather consistent age-related phenomenon in a normal population. Ranking might shed more light on the change in distribution of the SMPs than would quantification alone4.
This overview, as was our overview of normal motor development4, is limited by our choice to evaluate only a few items of motor assessment and focus on one main developmental aspect per fetus. However, both reviews reveal that fetal sonographic assessment should include various motor aspects. It is not only the quantitative data, though easy to reproduce, that give insight into motor changes, but also, or even more so, data on quality, emergence and differentiation of SMPs and behavioral states that are important. Which motor aspects change is dependent upon the underlying problem. Both overviews are meant to stimulate future research on various aspects of motor activity with reproducible methods. The next step could be the recommendation to make use of prenatal motor assessment procedures in future routine care. Since we are not yet able to discern fetuses at high risk for developing a motor handicap after birth, we must strive to increase the possibilities of the fetal neurological examination with respect to its functional expression of the CNS. A multidisciplinary approach facilitates linkage with neurological outcomes or possible postmortem findings.