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Objective: To describe the individual intrauterine growth patterns of fetuses of insulin-dependent (Type-1) diabetic women and to examine determinants of overgrowth (macrosomia) and its timing. Methods: This retrospective longitudinal study examined the developmental trajectories of fetal abdominal circumference (AC) and biparietal diameter in 76 Type-1 diabetic women with singleton pregnancies. Latent class analysis was used to identify subgroups of patients with a shared fetal AC growth trajectory. Subsequently, maternal factors, including glycemic control as assessed by glycosylated hemoglobin (HbA1c), were examined to see whether they had any effect on fetal growth. Results: Four subgroups with different AC growth patterns were identified. Differences in birth weight between the distinct subgroups were related to the shape of the AC growth velocity curve over gestation. Acceleration of AC growth commencing before or after 25 weeks' gestation was associated with the birth of a heavy or large-for-dates baby in 94 and 56% of cases, respectively. Poor glycemic control (HbA1c > 7.0%) during the periconception period or before 12 weeks' gestation was a modest predictor of midtrimester growth in AC. Other diabetes-related factors, fetal sex, parity, or maternal weight/obesity were unrelated to the fetal growth pattern. Conclusion: The findings suggest that an individual fetus's growth trajectory is set early in gestation and that the contemporaneous degree of maternal glycemia plays a role in determining birth weight. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Children's Communication Checklist (CCC; Bishop, 1998) is a questionnaire that was developed to measure pragmatic language use and may be completed by parents and teachers. Two studies are reported, which were designed to investigate: (1) whether children with Attention Deficit Hyperactivity Disorder (ADHD) encounter pragmatic language problems in comparison with normal controls (NC), (2) whether children with ADHD and children with High Functioning Autism (HFA) can be differentiated using the CCC, (3) the usefulness of the CCC for parents and teachers in a clinical and in a research setting, and (4) the role of age in pragmatic language use in ADHD and HFA. METHOD: In the first study (clinical sample) 50 children with ADHD, 50 children with HFA, and 50 NC were compared to each other using the CCC. In the second study (research sample) CCC data was gathered on 23 children with ADHD (without co-morbid disorders), 42 children with HFA, and 35 NC. RESULTS: Compared to NC, children with HFA showed pragmatic deficits on all CCC scales. Children with ADHD demonstrated deficits compared to NC as well. Moreover, the ADHD and HFA groups differed from each other on most of the scales. Discriminant analyses showed that CCC scales were relevant for case identification in these samples. Furthermore, profiles of impairment seen in children with HFA and ADHD did not vary with age. CONCLUSION: Pragmatic difficulties do occur in both HFA and ADHD. The present studies indicate that the CCC is a useful instrument to obtain information concerning pragmatic language use in both a clinical and a research setting. Although the information of parents is more tightly linked to the diagnosis, combining the information of both parent and teacher slightly improves case identification. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study investigated the interrelationship between psychopharmacotherapy in general and the use of specific psychotropic drugs and pervasive developmental disorder and other behavior problems in children and adolescents with mental retardation. METHODS: A total of 862 participants 4 to 18 years of age, including all levels of mental retardation, were recruited through facilities for children with mental retardation in Friesland, The Netherlands. Information on medication was collected through parent interviews. Behavior problems were investigated with a standardized parent questionnaire (Developmental Behavior Checklist). A pervasive developmental disorder classification was based on the Pervasive Developmental Disorder in Mental Retardation Scale, completed by psychologists or teachers. Logistic regression analysis was used to investigate the relationship between the use of psychotropic drugs and pervasive developmental disorder and other behavioral problems, in the presence of possible confounders. RESULTS: One of 10 participants used psychotropic medication. The main factors associated with psychotropic drug use were pervasive developmental disorder and disruptive behavior. The level of functioning was also associated. Self-absorbed behavior was statistically significantly associated with clonidine use and disruptive behavior with stimulant use. Pervasive developmental disorder and communication problems were the main factors associated with the use of antipsychotic drugs. Age also played a role, whereas gender, living situation, and level of mental retardation did not. CONCLUSIONS: Antipsychotic drugs were associated with pervasive developmental disorder, whereas clonidine and stimulants were associated with self-absorbed and disruptive behavior, respectively. Although clonidine and risperidone are not registered for the problems reported and the other nonstimulants were only sometimes used on-label, their use was associated with specific psychiatric or behavioral problems. [ABSTRACT FROM AUTHOR]

Here, we present a protocol to deliver nanoliter volumes of Toll-like receptor (TLR) agonist onto a culture of nuclear factor κB (NF-κB) reporter macrophages using fluidic force microscopy and a micron-scale probe. We describe steps for quantifying the dose of agonist by modeling their diffusion with experimental inputs. We then detail procedures for quantifying and categorizing macrophage responses to individual and varied doses and combining agonist concentration and macrophage response to analyze the NF-κB response to localized TLR stimulation. For complete details on the use and execution of this protocol, please refer to Mulder et al. (2024). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The innate immune system initiates early response to infection by sensing molecular patterns of infection through pattern-recognition receptors (PRRs). Previous work on PRR stimulation of macrophages revealed significant heterogeneity in single cell responses, suggesting the importance of individual macrophage stimulation. Current methods either isolate individual macrophages or stimulate a whole culture and measure individual readouts. We probed single cell NF-κB responses to localized stimuli within a naïve culture with Fluidic Force Microscopy (FluidFM). Individual cells stimulated in naïve culture were more sensitive compared to individual cells in uniformly stimulated cultures. In cluster stimulation, NF-κB activation decreased with increased cell density or decreased stimulation time. Our results support the growing body of evidence for cell-to-cell communication in macrophage activation, and limit potential mechanisms. Such a mechanism might be manipulated to tune macrophage sensitivity, and the density-dependent modulation of sensitivity to PRR signals could have relevance to biological situations where macrophage density increases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mulder, Moser, Delgado, Steinhardt and Esser-Kahn.)

Cationic polymers are widely used materials in diverse biotechnologies. Subtle variations in these polymers' properties can change them from exceptional delivery agents to toxic inflammatory hazards. Conventional screening strategies optimize for function in a specific application rather than observing how underlying polymer-cell interactions emerge from polymers' properties. An alternative approach is to map basic underlying responses, such as immunogenicity or toxicity, as a function of basic physicochemical parameters to inform the design of materials for a breadth of applications. To demonstrate the potential of this approach, we synthesized 107 polymers varied in charge, hydrophobicity, and molecular weight. We then screened this library for cytotoxic behavior and immunogenic responses to map how these physicochemical properties inform polymer-cell interactions. We identify three compositional regions of interest and use confocal microscopy to uncover the mechanisms behind the observed responses. Finally, immunogenic activity is confirmed in vivo . Highly cationic polymers disrupted the cellular plasma membrane to induce a toxic phenotype, while high molecular weight, hydrophobic polymers were uptaken by active transport to induce NLRP3 inflammasome activation, an immunogenic phenotype. Tertiary amine- and triethylene glycol-containing polymers did not invoke immunogenic or toxic responses. The framework described herein allows for the systematic characterization of new cationic materials with different physicochemical properties for applications ranging from drug and gene delivery to antimicrobial coatings and tissue scaffolds., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

With Latent Class Analysis applied on data of 98 children with autism spectrum disorder (ASD) (9-12 years; 17 girls) participating in social skills training (SST) in a randomized controlled trial (Dekker et al. 2019), four subgroups were detected, based on social-communicative skills before, and response patterns to training. Two subgroups improved after SST. Characterizing the subgroups based on participant and intervention characteristics showed that improvement was related to lower parent-reported perceived difficulty of social-communicative skills at start, higher verbal ability, younger age and milder symptoms of ASD and anxiety. The lowest performing non-improving subgroup participated more often in SST without parent/teacher involvement, compared to all other subgroups. Response to SST in ASD seems to vary depending on participant characteristics.

In 122 high-functioning children with autism spectrum disorder (ASD; 9-13 years; 19 girls), we investigated the effectiveness of a 15-session social skills group training (SST) with and without parent and teacher involvement (PTI) in a randomized controlled trial with three conditions: SST (n = 47), SST-PTI (n = 51), and care-as-usual (CAU, n = 24). Hierarchical linear modeling was used for immediate and 6-month follow-up analyses. Measures were administered before randomization (blind), post-treatment and at follow-up (not blind). Trial registration: Dutch Trial Register; http://www.trialregister.nl ; NTR2405. At post-treatment, children in both SSTs had improved significantly more than CAU on the primary outcome, Vineland Socialization (SST: Cohen's d = 0.39; 95% CI - 2.23 to 3.11 and SST-PTI: d = 0.43; 95% CI - 2.19 to 3.15) and on the secondary outcome parent-SSRS "Cooperation" (SST: d = 0.43; 95% CI - 0.23 to 1.15 and SST-PTI: d = 0.45; 95% CI - 0.21 to 1.17), with no difference between post-treatment and follow-up. Additionally, children in SST-PTI improved significantly more on the teacher-SSRS than in CAU ["Cooperation" d =0.42 (95% CI - 0.33 to 1.13); "Assertion" d =0.34 (95% CI - 0.39 to 1.11); "Self-Control" d =0.61 (95% CI - 0.08 to 1.34)] and in SST ["Cooperation" d =0.34 (95% CI - 0.37 to 1.05); "Self-Control" d =0.59 (95% CI - 0.13 to 1.32)]. The current study corroborates earlier findings in smaller samples and wider age ranges, with small but statistically significant effects of SST for high-functioning pre-adolescent children with ASD. Parental and teacher involvement intensified treatment, yet did not yield an additional effect relative to SST for children only, as reported by parents. 6 months after training, no further improvement or decline was found.

The Social skills Observation Measure (SOM) is a direct observation method for social skills used in naturalistic everyday situations in school. This study describes the development of the SOM and investigates its psychometric properties in 86 children with Autism spectrum disorder, aged 9.8-13.1 years. The interrater reliability was found to be good to excellent. The convergent validity was low in relation to parent and teacher reports of social skills, and also to parent interview on adaptive social functioning. Therefore this direct observation seems to provide additional information on the frequency and quality of social behaviors in daily life situations. As such it contributes to parent and teacher information as a blind measurement to evaluate Social Skills Training.

Objective: This study aimed to assess the accuracy of the ultrasonographic prediction of intertwin birth weight discordance based on crown-rump length, estimated fetal weight (EFW) and abdominal circumference., Method: We retrospectively studied variables of prenatal surveillance of 281 twin pregnancies at the University Medical Centre Utrecht, between 2008 and 2011., Results: Fifteen per cent of twins had a birth weight discordance of ≥20%. One twin more commonly had intrauterine growth restriction in the birth weight discordance group compared with the concordantly grown group (69% vs 20%, respectively). Sonographically, EFW discrepancy and increased abdominal circumference ratio were significantly correlated with birth weight discordance. The negative predictive values were high (92% and 87%, respectively). The best prediction of weight discordance was given by EFW discordance at the last ultrasound before delivery., Conclusion: Intertwin birth weight discordance is best predicted by an intertwin EFW discordance at the last ultrasound. If discordance is not suspected by ultrasound, the vast majority had no birth weight discordance. In case of birth weight discordance, the presence of at least one growth-restricted twin is very likely. However, because around 20% of concordantly grown twin pairs comprise at least one intrauterine growth restriction infant, one cannot rely on weight discordance alone., (© 2015 John Wiley & Sons, Ltd.)

Background: Social skills training (SST) is a common intervention for children with autism spectrum disorders (ASDs) to improve their social and communication skills. Despite the fact that SSTs are often applied in clinical practice, the evidence for the effectiveness of these trainings for children with ASD is inconclusive. Moreover, long term outcome and generalization of learned skills are little evaluated. Additionally, there is no research on the influence of involvement of parents and teachers on effectiveness of SST and on the generalization of learned social skills to daily life. We expect parent and teacher involvement in SST to enhance treatment efficacy and to facilitate generalization of learned skills to daily life., Method/design: In a randomized controlled trial (RCT) with three conditions, 120 participants with ASD at the end of primary school (10-12 years of calendar age) have been randomized to SST, SST-PTI (SST with Parent & Teacher Involvement), or care-as-usual. The SST consists of 18 group sessions of 1.5 hours for the children. In the SST-PTI condition, parents additionally participate in 8 parent sessions and parents and teachers are actively involved in homework assignments. Assessment takes place at three moments: before and immediately after the intervention period and at 6 months follow-up. Primary outcome is socialization, as an aspect of adaptive functioning. Secondary outcomes focus on specific social skills children learn during SST and on more general social skills pertaining to home and community settings from a multi-informant perspective. Additionally, possible predictors of treatment outcome will be assessed., Discussion: The current study is an RCT study evaluating SST in a large sample of Dutch children with ASD in a specific age range (10-12 years). Strengths of the study are the use of one manualized protocol, application of standardized and internationally used rating instruments, use of multiple raters, investigation of generalization of learned skills to daily life, and the evaluation of efficacy in the longer term by follow-up measures at 6 months after the end of training., Trial Registration: NTR2405.

Objectives: To determine whether there is an association between sonographically assessed hyper- or hypocoiling of the umbilical cord and the presence of trisomy 21, to provide reference values for the antenatal umbilical coiling index (aUCI) at a gestational age of 16-21 weeks and to determine whether these measurements are reliable and reproducible., Methods: This was a prospective study of 737 pregnancies in which the aUCI was measured between 16 and 21 weeks of gestation by ultrasound at the time of amniocentesis. The aUCI was calculated as the reciprocal value of the mean length of one complete coil in centimeters. We created reference curves and studied the relationship with trisomy 21 and other chromosomal defects. In 30 pregnancies we studied the intra- and interobserver variation in measurements using Bland-Altman plots with associated 95% limits of agreement and intraclass correlation coefficients., Results: aUCI was found to be non-linearly related to gestational age at 16-21 weeks and reference curves were created for the mean aUCI and the 2.3(rd) , 10(th) , 90(th) and 97.7(th) percentiles. There was no significant difference in aUCI values between the reference group (n = 714) and cases with trisomy 21 (n = 16) or other aneuploidies (n = 7) (one-way ANOVA, P = 0.716). There was good intra- and interobserver agreement in aUCI measurements., Conclusions: The aUCI can be measured reliably and varies according to gestational age at 16-21 weeks. The aUCI was not significantly associated with trisomy 21 or other chromosomal defects., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Increasingly, maternal administration of 17-α-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations., Methods: This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16-20 and 36 weeks' gestation., Results: The three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups., Conclusion: The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Fetal movements and fetal heart rate (FHR) are well-established markers of fetal well-being and maturation of the fetal central nervous system. The purpose of this paper is to review and discuss the available knowledge on fetal movements and heart rate patterns in twin pregnancies. There is some evidence for an association or similarity in fetal movement incidences or FHR patterns between both members of twin pairs. However, the temporal occurrence of these patterns seems to be for the most part asynchronous, especially when stricter criteria are used to define synchrony. The available data suggest that fetal behavior is largely independent of sex combination, fetal position, and presentation. Conversely, chorionicity appears to have some influence on fetal behavior, mainly before 30 weeks of gestation. There is preliminary evidence for the continuity of inter-individual differences in fetal activity and FHR patterns over pregnancy. Comparisons between studies are limited by large methodological differences and absence of uniform concepts and definitions. Future studies with high methodological quality are needed to provide a more comprehensive knowledge of normal fetal behavior in twin pregnancy.

Objective: To compare the effect of third trimester three-dimensional and four-dimensional (3D/4D) versus two-dimensional (2D) ultrasound (US) of the fetal face on maternal bonding. Studies quantifying the psychological effect of 3D/4D US on mothers, pregnant of a fetus with no detectable abnormalities, were reviewed., Methods: One hundred sixty Caucasian women attended a third trimester 3D/4D or 2D US examination. Women filled out the Maternal Antenatal Attachment Scale (MAAS) 1 to 2 weeks before (MAAS1) and 1 to 2 weeks after (MAAS2) the US examination. Visibility, recognition and attractiveness were assessed., Results: Within both US groups, the MAAS2 scores were significantly higher than the MAAS1 scores (p < 0.0001). No differences in MAAS scores between the US groups emerged. Visibility and recognition were significantly positively related with the increase in MAAS scores (p = 0.003 and p = 0.042) in the 3D/4D group. Of 13 psychological studies, eight studies evaluated bonding and found no difference between 3D/4D and 2D US. The effect of 3D/4D US on satisfaction or perception showed conflicting results, and on anxiety/stress, reduction was the same as after 2D US., Conclusions: Bonding increases after either a 3D/4D or 2D US. The effect of 3D/4D US on bonding is stronger at better degrees of visibility and recognition., (© 2012 John Wiley & Sons, Ltd.)

Objective: To study fetal heart rate (FHR), its short term variability (STV), average acceleration capacity (AAC), and average deceleration capacity (ADC) throughout uncomplicated gestation, and to perform a preliminary comparison of these FHR parameters between small-for dates (SFD) and control fetuses., Methods: Prospective observational study of 7 h FHR-recordings obtained with a fetal-ECG monitor in the second half of uncomplicated pregnancies (n = 90) and pregnancies complicated by fetal SFD (n = 30). FHR and STV were calculated according to established analysis. True beat-to-beat FHR, recorded at 1 ms accuracy, was used to calculate AAC and ADC using Phase Rectified Signal Averaging (PRSA). Mean values of FHR, STV, AAC, and ADC derived from recordings in SFD fetuses were compared with the reference curves., Results: Compared with the control group the mean z-scores for STV, AAC, and ADC in SFD fetuses were lower by 1.0 SD, 1.5 SD, and 1.7 SD, respectively (p < 0.0001 for all comparisons). In SFD fetuses, both the AAC and ADC z-scores were lower than the STV z-scores (p < 0.02 and p < 0.002, respectively)., Conclusions: Analysis of the AAC and ADC as recorded with a high resolution fECG recorder may differentiate better between normal and SFD fetuses than STV.

Objective: In a refugee camp on the Thai-Burmese border, accurate dating of pregnancy relies on ultrasound measurements obtained by locally trained health workers. The aim of this study was to substantiate the accuracy of fetal biometry measurements performed by locally trained health workers by comparing derived reference equations with those published for Asian and European hospitals., Methods: This prospective observational study included 1090 women who had a dating crown-rump length (CRL) scan and one study-appointed ultrasound biometry scan between 16 and 40 weeks of gestation. The average of two measurements of each of biparietal diameter, head circumference, abdominal circumference and femur length was used in a polynomial regression model for the mean and SD against gestational age (GA). The biometry equations obtained were compared with published equations of professional sonographers from Asian and European hospitals by evaluation of the SD and Z-scores of differences between models., Results: Reference equations of biometric parameters were found to fit cubic polynomial models. The observed SD values, for any given GA, of fetal biometric measurements obtained by locally trained health workers were lower than those previously reported by centers with professional sonographers. For nearly the entire GA range considered, the mean values of the Asian and European equations for all four biometric measurements were within the 90% expected range (mean ± 1.645 SD) of our equations., Conclusion: Locally trained health workers in a refugee camp on the Thai-Burmese border can obtain measurements that are associated with low SD values and within the normal limits of published Asian and European equations. The fact that the SD values were lower than in other studies may be explained by the use of the average of two measurements, CRL dating or motivation of the locally trained sonographers., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Motility assessment before birth can be used to evaluate the integrity of the nervous system. Sideways bending (SB) of head and/or rump, the earliest embryonic motility in both humans and guinea pigs, can be visualized sonographically. We know from other species that early embryonic motility is cyclic. This study explores the distribution of SB-to-SB intervals in human and guinea pig embryos before the appearance of more complex movements such as general movements. We hypothesized that the activity in both species is cyclic. We made 15-min sonographic recordings of SBs between 5 weeks and 0 days (5wk0d) and 7wk0d conceptional age (CA) in 18 human embryos of uncomplicated IVF pregnancies (term 38 weeks) and in 20 guinea pig embryos between 3wk4d and 4wk0d CA (term 9 weeks). SB-to-SB interval durations were categorized as long (≥10 s) or short (<10 s) intervals. For human embryos, the median values for long and short intervals were 61 s (range, 10-165 s) and 3 s (range, 1-9 s) respectively; for guinea pigs 38 s (range, 10-288 s) and 5 s (range, 1-9 s), respectively. During development, the duration of long intervals decreased while the number of short intervals increased for both species. The earliest embryonic motility in the human and guinea pig is performed cyclically with distinct developmental milestones. The resemblance of their interval development offers promising possibilities to use the guinea pig as a noninvasive animal model of external influences on motor and neural development., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound., Methods: Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses., Results: Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies., Conclusion: The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.

Objectives: A prospective study was performed to compare fetal behavioral development in healthy dichorionic twins and singletons, and identify twin intra-pair associations (synchrony) of fetal movements and rest-activity cycles using different criteria to define synchrony., Subjects and Methods: Twenty pregnant women carrying dichorionic twins participated. Serial simultaneous 1-hr recordings of fetal movements were made on twins between 11 and 40 weeks' gestation (wGA) using two ultrasound machines. All twins were born healthy after 36 wGA and of appropriate weight for gestation. The incidences of fetal generalized body movements (GM) and breathing movements in twins were compared with institutional reference values for singletons. A comprehensive smoothing procedure on the raw movement data was performed to evaluate previously reported variation in twin intra-pair synchrony., Results: Twin fetuses were less active (GM) than singletons throughout pregnancy, but their breathing activity was higher in the third trimester. The incidences of fetal GM, quiescence, and breathing were fairly correlated within twin pairs. However, the temporal association or simultaneous occurrence of these activities was poor, especially after 30 weeks' gestation, coinciding with emerging rest-activity cycles. There was no evidence of a consistently more active ('dominant') twin half. Potential confounders had no effect on behavioral development in fetal twins., Conclusions: The results show differential behavioral development between normal dichorionic fetal twins and singletons. Within fetal twin-pairs, we found poor synchrony of movements and independent occurrence of rest-activity cycles. Previous research on fetal twin behavior appears to have overestimated the degree of intra-pair movement synchrony., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Fetal sleep states emerge during the third trimester of pregnancy and involve multiple interconnected neuronal networks. We examined whether fetal sleep characteristics predict child and adolescent self-regulation in a non-clinical sample (study group, n=25; reference group, n=48). Combined recordings of three sleep variables (fetal heart rate, body movements and rapid eye movements) were made for 2 h at 36-38 weeks' gestation. Fetuses showing synchronous change of sleep variables (i.e. within 3 min) at transition from quiet into active sleep reached a higher level of effortful control, both at 8-9 and 14-15 years, than fetuses not making synchronous transitions and compared with the reference group. Results are discussed from a Developmental Origins of Behavior, Health and Disease (DOBHaD) point of view. It is concluded that studying sleep ontogeny offers the possibility to gain insight into brain maturational processes and/or environmental adaptive processes that may have long term behavioral developmental consequences., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The rooting reflex has long been studied by neurologists and developmentalists and is defined as an orientation toward tactile stimulation in the perioral region or visual stimulation near the face. Nearly, all previous reports of the visual rooting reflex (VRR) concern its presence in adults with neurological dysfunction. Previously, the VRR was reported to be present in a majority of individuals with autism and absent in control subjects. In the present larger study, we examined the presence of the VRR in 155 individuals with ASD and co-occurring Intellectual Disability (ASD + ID: autism, N = 60; Pervasive Developmental Disorder-Not Otherwise Specified (PDD&#95;NOS), N = 95) and in a contrast group of 65 individuals with ID only. The VRR was present significantly more often in the ASD + ID (43.9%) group than in the ID-only group (24.6%; χ(1)(2)= 7.19; P = 0.007). Individuals with autism displayed a VRR more often (55.0%) than individuals with PDD-NOS (36.8%; χ(1)(2)= 4.92; P = 0.026) and individuals with ID only (24.6%; χ(1)(2)= 12.09; P = 0.001). A positive VRR was associated with lower IQ and adaptive functioning; in the ASD + ID group, ADI-R/ADOS domain scores were significantly higher in the VRR-positive subgroup. The results replicate and extend the finding of an increased occurrence of the VRR in autism. Although some association with IQ was observed, the VRR occurred substantially more often in the autism group compared with an intellectually disabled group, indicating some degree of specificity. Additional studies of infants and children with typical development, ASD and ID are needed to determine the utility of the VRR in ASD risk assessment and to elucidate possible specific behavioral associations., (Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.)

Purpose: To establish new cross-sectional reference values for the size of the lateral ventricles in a large cohort of neonates between 24 and 42 weeks' gestational age (GA) as well as longitudinal reference values for the follow-up of very preterm infants born at less than 30 weeks' gestation., Materials and Methods: Institutional review board approval and parental written informed consent were obtained for this prospective cohort study of 625 neonates (58% male patients) with a median GA of 33.4 weeks (range, 24.7-42.6 weeks). All infants underwent cranial ultrasonography (US) within 4 days after birth to evaluate the size of the lateral ventricles. Scanning was repeated in 301 preterm and term neonates within the 1st week of life to assess the presence of ventricular reopening. Seventy-nine very preterm infants (GA, <30 weeks) were prospectively included for cranial US at term-equivalent age (TEA). US measurements were performed of the ventricular index (VI), anterior horn width (AHW), and thalamo-occipital distance (TOD). Statistical analysis was conducted by using a paired t test, multilevel analysis, and analysis of covariance., Results: Cross-sectional reference values for the VI and TOD increased with maturity, whereas the AHW remained constant. Vaginal birth was independently associated with a slightly smaller AHW following birth and with an increase in AHW within the 1st week of life (P < .05). Preterm-born infants showed a larger ventricular size at TEA compared with term infants (P < .001)., Conclusion: New cross-sectional and longitudinal reference curves were established for the size of the neonatal lateral ventricles, which may allow for early identification and quantification of ventriculomegaly due to either posthemorrhagic ventricular dilation or periventricular white matter loss., (© RSNA, 2011.)

The aim of this prospective study was to investigate whether selective serotonin reuptake inhibitors (SSRIs) utilized by pregnant women influence fetal neurobehavioral development. In this observational study we investigated developmental milestones of fetal behavior during the pregnancy of women with psychiatric disorders who took SSRIs throughout gestation (medicated group; n=96) or who had discontinued medication early in gestation or before conception (unmedicated group; n=37). Healthy unexposed fetuses of women without mental disorders comprised the control group (n=130). Ultrasonographic observations of fetal behavior were made three times in pregnancy (T1-T3). Effects of SSRIs were studied over a wide range of dosages (low, standard, or high) and for different drug types. Fetuses exposed to standard or high SSRI dosages compared with control, unmedicated, or low-medicated fetuses showed significantly increased motor activity at the beginning (T1) and end of the second trimester (T2). They particularly exhibited disrupted emergence of non-rapid eye movement (non-REM; quiet) sleep during the third trimester, characterized by continual bodily activity and, thus, poor inhibitory motor control during this sleep state near term (T3). The SSRI effects on the fetus were dose related, but independent of SSRI type. The results demonstrate changes in fetal neurobehavioral development associated with standard and high SSRI dosages that are observable throughout gestation. A first-choice SSRI type was not apparent. Bodily activity at high rate during non-REM sleep in SSRI-exposed fetuses is an abnormal phenomenon, but its significance for postnatal development is unclear.

Objective. Hourly fetal urine production rate (HFUPR) was studied in relation to both gestational age and the onset of spontaneous labor in normal term human pregnancies. Methods. Serial volume measurements were obtained from longitudinal ultrasound images of the fetal bladder at 1-5-minute intervals, and HFUPR was subsequently calculated. A total of 178 adequate bladder-filling cycles were recorded in 112 women, and the amniotic fluid index (AFI) was assessed. Results. HFUPR did not change significantly between 37 and 42 weeks' gestation. However, HFUPR decreased during the last 14 days prior to the onset of spontaneous labor (P < 0.005). No significant correlation was found between HFUPR and AFI, neither when measured at the same time nor when HFUPR and AFI were measured at various intervals in time. Conclusion. HFUPR falls before and in relation to the time of onset of labor rather than in relation to gestational age.

Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70  mg/day) in 32 youths with pervasive developmental disorder (mean age = 8.74, range = 5-16 years) in relation to -759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 ± 0.017 body mass index-standardized z scores (1.84 ± 1.51  kg) versus 0.64 ± 0.35 z (3.23 ± 1.47  kg) for non-T-allele carriers (p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the -759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain.

Little is known about the effect on the human foetus of long-term and acute exposure to caffeine. We studied the organisation of foetal sleep-wake states in 13 healthy near-term foetuses over a wide range of maternal plasma caffeine concentrations (0-13 μg/mL) reflecting normal lifestyle conditions (day 0) and again following intake of two cups of regular coffee (~300 mg of caffeine) intermitted by 50 h of abstinence (day 2; acute effects). On either day, 2 h simultaneous recordings were made of foetal heart rate, general-, eye-, and breathing-movements. The recordings were analysed for the presence of each of four foetal behavioural states: quiet- and active-sleep, quiet- and active-wakefulness. There was a linear relationship between maternal caffeine content and the incidence of foetal general movements during active sleep on day 0 (R = 0.74; P < 0.02). After coffee loading on day 2, foetuses of non- or low-caffeine consumers showed increases in active wakefulness (P < 0.001), general movements (P < 0.05) and heart rate variation (P < 0.01) but lower basal heart rate (P < 0.01) compared with their day 0 values. The changes in foetal heart rate (variation) and behaviour occurred between 90 and 180 min post-consumption. In contrast, foetuses of habitual caffeine consumers remained unaffected suggestive of foetal tolerance to caffeine. The results indicate differential performance between foetuses regularly exposed to caffeine and those caffeine-naive, both under normal maternal lifestyle conditions and in response to maternal coffee ingestion.

Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 x 10(-5)) and between SND1 and strict autism (rs1881084, P=7.76 x 10(-5)) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1.

Preterm birth is strongly associated with neonatal death and long-term neurological morbidity. The purpose of tocolytic drug administration is to postpone threatening preterm delivery for 48 hours to allow maximal effect of antenatal corticosteroids and maternal transportation to a center with specialized neonatal care facilities. There is uncertainty about the value of atosiban (oxytocin receptor antagonist) and nifedipine (calcium channel blocker) as first-line tocolytic drugs in the management of preterm labor. For nifedipine, concerns have been raised about unproven safety, lack of placebo-controlled trials, and its off-label use. The tocolytic efficacy of atosiban has also been questioned because of a lack of reduction in neonatal morbidity. This review discusses the available evidence, the pros and cons of either drug and aims to provide information to support a balanced choice of first-line tocolytic drug: atosiban or nifedipine?

Objective: To examine the relative importance of antenatal and perinatal variables on short- and long-term outcome of preterm growth restricted fetuses with umbilical artery (UA) Doppler abnormalities., Methods: This was a cohort study of 180 neonates with birth weight < 10(th) percentile, gestational age at delivery < 34 weeks and abnormal Doppler ultrasound examination of the UA. Various antenatal and perinatal variables were studied in relation to short- and long-term outcome., Results: Neonatal and overall mortality (up to 2 years of age) were predicted by low gestational age at delivery. Neonatal mortality was additionally predicted by absent or reversed UA end-diastolic flow, while the presence of severe neonatal complications and placental villitis were additional predictors of both infant (between 28 days and 1 year of postnatal life) and overall mortality. Placental villitis was found to be the only predictor of necrotizing enterocolitis. Low gestational age at delivery, male sex, abnormal cardiotocography, absent or reversed UA end-diastolic flow and the HELLP syndrome predicted respiratory distress syndrome. Abnormal neurodevelopmental outcome at 2 years was predicted by low birth weight (< 2.3(rd) percentile), fetal acidosis (UA pH < 7.00), and placental villitis., Conclusion: Less advanced gestation at delivery remains an important predictor of short-term outcome in growth-restricted fetuses. In addition, the presence of placental villitis may aid neonatologists in the early identification of infants at increased risk of necrotizing enterocolitis, death and abnormal neurodevelopment at 2 years of age. Abnormal neurodevelopment was related to low weight and acidosis at birth, indicating that the severity of malnutrition and fetal acidosis affect long-term outcome.

The obesity epidemic challenges traditional antenatal fetal heart rate (FHR) monitoring technologies. Doppler signals in particular are attenuated. We sought to evaluate whether the performance of a novel transabdominal fetal electrocardiogram (fECG) device (AN24, Monica Healthcare) is influenced by body mass index (BMI). We performed a prospective observational study of singleton pregnancies (gestational age [GA] 20 to 41 weeks) monitored overnight with fECG. Recording quality ([RQ] %) of both the best hour and the total recording time of the FHR record were related to BMI. Two hundred four women were monitored. BMI ranged from 16.0 to 50.7 (median BMI 26.9). The correlation coefficient (with 95% confidence interval [CI]) between BMI and RQ was -0.35 (CI -0.60; -0.03) for the gestational age group 20(+0) to 25(+6) weeks, -0.08 (CI -0.28; 0.13) for GA 26(+0) to 33(+6) weeks, and -0.20 (CI -0.40; 0.03) for GA group > or =34(+0) weeks. Median RQ in obese women (BMI > or =30 kg/m(2)) was 97.4, 98.9, and 100%, respectively. BMI has no clinically significant influence on recording quality of FHR monitored with fECG. It can therefore be considered a good method for monitoring the fetal condition in pregnancies of obese women., (Copyright Thieme Medical Publishers.)

Repeated ultrasonographic observation of fetal movements was used to distinguish movement patterns and to investigate the rate of occurrence and temporal organisation of these patterns (rest-activity cycles) during the last three weeks of gestation in the pig. By means of transabdominal ultrasonography with a 3.5MHz linear array transducer, motility in ten different fetuses (one per sow) was studied. Six (median; range 4-6) 1h recordings were made per fetus at 3-5 day intervals. Fifty-five 1h recordings were available for analysis. The occurrence of fetal general movements (GM), isolated head (HM), forelimb movements (LM), and rotations (ROT) was analysed from video tapes. For each movement pattern, the trend in occurrence over time was assessed by multilevel analysis. The temporal association between different movement patterns was studied by calculation of the kappa value. ROT occurred very infrequently and showed no particular trend over time. GM, HM, and LM showed a significant decreasing trend towards parturition (P<0.01). Total fetal activity (i.e., the sum of the four movement incidences) declined from an average of 25% of recording time to 9% over the last three weeks of pregnancy. Periods of fetal quiescence gradually increased with progressing gestation (P<0.05). There was no evidence of concordant association between the periods of rest and activity of GM, HM, and LM or of improved temporal linkage between these movement patterns with time. Fetal bodily activity decreases towards parturition mainly due to prolonged periods of rest. Fetal movement patterns show rest-activity cycles, but each pattern appears to cycle independently from the other throughout late gestation. The present results of spontaneous fetal movements in the pig provide reference data for future studies of fetal activity under different zoo technical conditions or pharmacological interventions.

Background: Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs., Methods: In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls., Results: Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3., Conclusions: Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.

Objective: A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production., Methods: Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined., Results: In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups., Conclusions: The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production., ((c) 2009 S. Karger AG, Basel.)

Assessment of fetal motility is an approach to evaluate the development and function of the nervous system before birth. Reference values for the time of first occurrence and the incidence of normal fetal movements are indispensable for studies in which prenatal motor activity is applied as a model to study the central and peripheral nervous systems. Studies on fetal motility have been performed in a few species, particularly in the human. The aim of the present study is to describe the ontogeny of fetal motility in the guinea pig, a precocious polytocous species. After a pilot study to establish procedures for repeated ultasonographic scanning of guinea pigs, 10 domesticated animals were scanned (5.0 or 7.5 MHz convex transducer) at 2-4 day intervals between day 24 and 63 of gestation (term age 68 days). Per animal two selected fetuses were each scanned for 15 min. Images were stored on videotape and analyzed off-line for the first onset, presence and quality of fetal movement patterns, and quantity of sideway bendings, general movements, breathing movements and periods of fetal rest. Twenty-five different movement patterns could be characterized, 6 emerging at the onset of motor activity were performed only temporarily. The very first fetal movement was observed on day 24 gestational age, and subsequently most other movements developed during a period of only 5 days. Interfetal difference in onset of the frequently occurring sideway bendings, general movements, and front and hind limb movements was only 2 days. Sideway bendings and general movements co-existed during days 29 to 43. There were developmental trends in the course of pregnancy. Sideway bendings increased rapidly between 24 and 30 days and declined hereafter. General movements and fetal breathing increased during midpregnancy and declined towards parturition. Conversely, fetal rest was observed for approximately 60% of time at midgestation and a marked increase was found towards parturition. There were no significant differences in developmental trend of the various movement patterns between individual fetuses. Fetal motility in the guinea pig followed a specific temporal pattern, like in the human, but at a different time scale. The present quantitative data will enable functional investigations into the role of the neuromuscular system. They may also facilitate studies on the effect of environmental influences, such as stress, drugs, toxic substances, and food conditions, on fetal neurobehavioural development in this species.

Objective: To determine which prenatal ultrasound findings can predict survival and mental and motor functioning in children with spina bifida., Methods: Prenatal ultrasound examinations of all liveborn children who were prenatally diagnosed with spina bifida between 1997 and 2002 at the University Medical Centre, Utrecht (n = 41) were retrospectively reviewed for lesion level, head circumference, ventriculomegaly, scoliosis and talipes. These measures were correlated with postnatal anatomical (as assessed by magnetic resonance imaging (MRI)) and functional lesion levels, survival and motor and mental outcome at 5 years of age. The capacity of prenatal ultrasonography to determine lesion level was also assessed in all fetuses diagnosed with spina bifida from 2006-2007 (n = 18)., Results: Nineteen infants died before the age of 5 years. Multivariate regression analysis showed that higher lesion level and head circumference > or = the 90th percentile on prenatal ultrasound examination were independent predictors of demise (P < 0.05 and P = 0.01, respectively). None of the ultrasound features was a predictor of motor or mental functioning. Ultrasound predicted anatomical lesion level within one level of the postnatal findings in 50% of the first cohort and 89% of the second cohort (P < 0.01). The level of the anatomical lesion as assessed by postnatal MRI differed from the functional lesion by as many as six vertebral levels., Conclusions: Lesion level and head circumference on prenatal ultrasound are predictive of survival in children with spina bifida. No predictors were found for mental or motor function at the age of 5 years.

The purpose of this prospective longitudinal study was to evaluate the growth of the fetal cerebellar volume by means of 3-D ultrasound to evaluate whether there is a difference between the volumes of the left and right cerebellar hemispheres, and to evaluate the intra- and interobserver reliability of two different techniques of volume measurement. Three-dimensional ultrasound examinations were performed every two to three weeks on 27 fetuses between 20 and 40 weeks' gestation. Measurements of the total cerebellar volume and of the left and right cerebellar hemispheres were done using the multiplanar technique. Multilevel analysis was used to determine the growth of cerebellar volume based on individual developmental trajectories and compare the volume of the right and left hemispheres of the cerebellum. The intra- and interobserver reliability was calculated for the multiplanar and VOCAL techniques in a subgroup of 10 fetuses. A nonlinear growth curve of cerebellar volume in normal pregnancy was generated. The cerebellar growth per two-week decreased from a gain of 51% of the first measurement at 20 weeks to a gain of 16% of the first measurement at 38 weeks. The left cerebellar hemisphere was significantly larger (12.3%, p < 0.01) than the right. The intraclass correlation coefficient for the measurements by the two techniques was 0.99. Intraobserver reliability: the intraclass correlation coefficient for the measurements using the multiplanar technique was 0.96 and 0.97 and for VOCAL it was 0.98 and 0.97 for the two observers, respectively. Interobserver reliability: the intraclass correlation coefficient for the measurements using the multiplanar technique was 0.97 and for VOCAL 0.98. Longitudinal growth curves based on individual developmental trajectories were generated for the cerebellar volume. The left fetal cerebellar hemisphere was found to be significantly larger than the right. Both multiplanar and VOCAL techniques had a good intra- and interobserver reliability and yielded very similar results.

Objective: We studied psychological outcomes and predictors for adverse outcome in 147 women 4, 8, and 16 months after termination of pregnancy for fetal anomaly., Study Design: We conducted a longitudinal study with validated self-completed questionnaires., Results: Four months after termination 46% of women showed pathological levels of posttraumatic stress symptoms, decreasing to 20.5% after 16 months. As to depression, these figures were 28% and 13%, respectively. Late onset of problematic adaptation did not occur frequently. Outcome at 4 months was the most important predictor of persistent impaired psychological outcome. Other predictors were low self-efficacy, high level of doubt during decision making, lack of partner support, being religious, and advanced gestational age. Strong feelings of regret for the decision were mentioned by 2.7% of women., Conclusion: Termination of pregnancy for fetal anomaly has significant psychological consequences for 20% of women up to > 1 year. Only few women mention feelings of regret.

Antenatal corticosteroid therapy to enhance fetal lung maturity in threatened preterm delivery has a number of non-pulmonary side-effects, both beneficial and undesirable. This review focuses on the short-term (transient) effects of betamethasone and dexamethasone on aspects of fetal circulation and behaviour which are used clinically as markers of fetal well-being. We summarise the effects observed, discuss the proposed underlying mechanisms, and emphasise the consequences for clinical decision-making. Recommendations are given to optimise medical care and to minimise the risk of unwarranted iatrogenic preterm delivery.

Background: The choice of first-line tocolytic agent is a topic of worldwide debate. The oxytocin receptor antagonist atosiban and the calcium antagonist nifedipine appear to be effective in postponing delivery. However, information is lacking on their possible effects on the fetal biophysical profile., Objective: To study the direct fetal effects of tocolysis with atosiban or nifedipine combined with a course of betamethasone., Method: We performed a randomised controlled study including women with preterm labour requiring tocolytic treatment. Primary outcome measures were the effects on fetal heart rate (FHR) and its variation. Secondary endpoints were the effects on fetal movement and blood flow (pulsatility index - PI) of the umbilical (UA) and medial cerebral arteries (MCA)., Results: One-hour recordings of FHR and fetal movements were made on each of five successive days (days 0-4). Fetal blood flow velocity patterns were studied daily by Doppler ultrasound. Baseline characteristics of 31 women who had not delivered at day 0 and needed no escape tocolysis did not differ between the study groups. Multilevel analysis showed no significant effect of either tocolytic on FHR and movement parameters over the 5-day study period. The use of tocolytics also did not significantly alter the time courses of PI-values for UA (p = 0.37) and MCA (p = 0.62)., Conclusion: This study demonstrates for the first time the direct effects of atosiban on fetal movement, heart rate and blood flow. Tocolysis with either atosiban or nifedipine combined with betamethasone administration appears to have no direct fetal adverse effects.

The feasibility and accuracy of long-term transabdominal fetal electrocardiogram (fECG) recordings throughout pregnancy were studied using a portable fECG monitor. Fifteen-hour recordings of fetal heart rate (FHR) were performed in 150 pregnant women at 20-40 weeks of gestation and 1-hour recordings were performed in 22 women in labour and compared with simultaneous scalp electrode recordings. When >or=60% of fECG signals was present, the recording was defined as good. Eighty-two percent (123/150) of antenatal recordings were of good quality. This percentage increased to 90.7 (136/150 recordings) when only the night part (11 p.m.-7 a.m.) was considered. Transabdominal measurement of FHR and its variability correlated well with scalp electrode recordings (r=0.99, P<0.01; r=0.79, P<0.01, respectively). We demonstrated the feasibility and accuracy of long-term transabdominal fECG monitoring.