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Objectives: To establish reference curves of normal fetal small bowel and colon diameters and to assess the clinical applicability.Method: Serial longitudinal ultrasound examinations at 4-week intervals between 20 to 41 weeks of gestation in 39 low-risk fetuses. The largest loop of the small bowel and colon was identified. The bowel lumen short axis was measured. Linear mixed modeling was used to determine individual developmental trajectories. Twenty-eight fetuses with suspected bowel dilatation were analyzed relative to the reference curves.Results: Development of the small bowel and colon diameters was best described by a linear and cubic model, respectively. The intraobserver and interobserver concordance were >0.94. In cases with suspected bowel dilatation, normal fetal outcome occurred if the bowel dilatation was transient. Progressive increase of fetal bowel diameter was associated with pathology after birth. Cases with small bowel pathology had a z-score >8 after 25 weeks of gestation.Conclusion: We provided the first ultrasound reference curves for normal fetal small bowel and colon diameters. Progressive increase in the fetal bowel diameter z-score was highly predictive of intestinal abnormalities after birth. Longitudinal follow-up of dilated fetal bowel is important to distinguish normality from disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term neurodevelopmental and behavioral outcome of antenatal allopurinol treatment during suspected fetal hypoxia. Study design: We studied children born from women who participated in a randomized double-blind placebo controlled multicenter study (ALLO-trial). Labouring women in whom the fetus was suspected to have fetal hypoxia were randomly allocated to receive allopurinol or placebo. At 5 years of age, the children were assessed with 2 parent reported questionnaires, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL). A child was marked abnormal for ASQ if it scored below 2 standard deviation under the normative mean of a reference population in at least one domain. For CBCL, a score above the cut-off value (95th percentile for narrowband scale, 85th percentile for broadband scale) in at least one scale was marked as abnormal. Results: We obtained data from 138 out of the original 222 mildly asphyxiated children included in the ALLO-trial (response rate 62%, allopurinol n = 73, placebo n = 65). At 5 years of age, the number of children that scored abnormal on the ASQ were 11 (15.1%) in the allopurinol group versus 11 (9.2%) in the placebo group (relative risk (RR) 1.64, 95% confidence interval (CI): 0.64 to 4.17, p = 0.30). On CBCL 21 children (30.4%) scored abnormal in de allopurinol group versus 12 children (20.0%) in the placebo group (RR 1.52, 95% CI: 0.82 to 2.83, p = 0.18). Conclusion: We found no proof that allopurinol administered to labouring women with suspected fetal hypoxia improved long-term developmental and behavioral outcome. These findings are limited due to the fact that the study was potentially underpowered. Trial registration: Dutch Trial Register NTR1383 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of prenatal neurosonography in diagnosing underlying causes of fetal ventriculomegaly, posterior fossa anomalies and microcephaly before 24 weeks' gestational age (GA) and to study the accuracy of prenatal counseling on postnatal prognosis.Methods: A retrospective cohort study based on 146 cases of these fetal brain anomalies before 24 weeks' GA. Counseling on prognosis was compared with postnatal outcome. Data on genetic testing was analyzed.Results: Out of 146 cases, 135 (92%) were diagnosed correctly before 24 weeks' GA. Accuracy was 98% (97/99) in cases with multiple anomalies and 81% (38/47) in cases with an isolated abnormality. Counseling on prognosis was correct in 143 out of 146 cases (98%). Prenatal genetic diagnostics detected an anomaly in 51/113 (45%) of cases. In 14/62 (23%) cases prenatal karyotyping was normal, but postnatal array-CGH detected a pathogenic anomaly.Conclusions: Despite the challenges of early gestation, accuracy in diagnosing and counseling fetal brain anomalies before 24 weeks' GA was high. Prenatal genetic testing is a valuable diagnostic tool and should be offered to all women with fetal brain anomalies. Considering the many different types of anomalies and diverse etiologies, a multidisciplinary approach is essential for counseling on postnatal outcome. [ABSTRACT FROM AUTHOR]

Objectives: There is evidence that in fetuses with congenital heart defects (CHDs), head growth is affected. However, scanty data are available on longitudinal growth patterns of other biometric parameters such as abdominal circumference (AC) and femur length (FL). The aim was to evaluate growth patterns in fetuses with isolated CHD diagnosed prenatally in different categories of lesions.Methods: Fetuses with isolated CHD seen between 2008 and 2013 at the Fetal Medicine Unit of 2 tertiary referral centers were retrospectively included in the study. CHD was classified into 7 categories. Fetal biometry parameters were assessed at 4 variable time points between 18 and 35 weeks' gestation and transformed into Z scores. Linear mixed modeling was performed to analyze repeated measurements and construction of growth models.Results: Two hundred forty-six live births with CHD were analyzed. Linear growth modeling showed a slight decrease in head circumference (HC) in the second half of pregnancy, whereas AC and FL growth were not significantly affected. The model predicted a significantly smaller HC at 36 weeks' gestation in fetuses with conotruncal heart defects.Conclusions: Fetuses with CHD showed a modest but significant linear decrease in HC growth, whereas AC and FL growth trajectories remained stable. [ABSTRACT FROM AUTHOR]

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 34+0 weeks. Median RQ in obese women (BMI 30 kg/m2) 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. [ABSTRACT FROM AUTHOR]

This is the first study to address the decision process of women who terminated their pregnancies after receiving a prenatal diagnosis of Down syndrome. [ABSTRACT FROM AUTHOR]

Objective: To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach-bladder distance, using three-dimensional (3D) ultrasound., Methods: This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography-based Automated Volume Count. The shortest stomach-bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach-bladder distance., Results: We included 79 affected fetuses. Sixty-six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach-bladder distance decreased (both P < .001). The developmental changes did not differ significantly between fetuses with simple and complex gastroschisis, neither for fetal stomach volume (P = .85), nor for stomach bladder distance (P = .78)., Conclusion: Fetal stomach volume and stomach-bladder distance, measured during pregnancy using 3D ultrasonography, do not predict complex gastroschisis., (© 2019 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Although the evidence regarding the benefit of using ST waveform analysis of the fetal electrocardiogram is conflicting, ST waveform analysis is considered as adjunct to identify fetuses at risk for asphyxia in our center. Most randomized controlled trials and meta-analyses have not shown a significant decrease in umbilical metabolic acidosis, while some observational studies have shown a gradual decrease of this outcome over a longer period of time. Observational studies can give more insight into the effect of implementation of the ST technology in daily clinical practice., Objective: To evaluate the change in frequency of perinatal intervention and adverse neonatal outcome after the implementation of ST waveform analysis of the fetal electrocardiogram from 2000 to 2013., Study Design: This retrospective longitudinal study was conducted in a tertiary referral center. A total of 19,664 medium- and high-risk singleton pregnancies with fetuses in cephalic presentation, a gestational age of ≥36 weeks, and the intention to deliver vaginally were included. ST waveform analysis of the fetal electrocardiogram was implemented in the year 2000 and by 2010 all deliveries were monitored using this technology. Data were collected on the following perinatal outcomes: fetal blood sampling, mode of delivery, umbilical cord blood gases, Apgar scores, neonatal encephalopathy, and perinatal death. Longitudinal trend analysis was used to detect changes over time in all deliveries monitored by cardiotocography either alone or in adjunct to ST waveform analysis of the fetal electrocardiogram. Logistic regression was used to correct for possible confounders., Results: The umbilical artery metabolic acidosis rate declined from 2.5% (average rate of 2000 + 2001 + 2002) to 0.4% (average of 2011 + 2012 + 2013) (P < .001), which represents an 84% decrease. This decrease largely occurred between 2006 and 2008, during the Dutch randomized trial on fetal electrocardiogram ST waveform analysis. At this time, approximately 20% of deliveries were monitored using this method. Furthermore, there were significant reductions in fetal blood sampling rate (P < .001). Overall cesarean and vaginal instrumental deliveries decreased significantly (P < .001), but not for fetal distress. There were no changes in the Apgar scores. The incidence of neonatal encephalopathy was significantly lower in the second part of the study (odds ratio 0.39, 95% confidence interval 0.17-0.89)., Conclusion: There was an 84% decrease in the incidence of umbilical artery metabolic acidosis in all deliveries between 2000 and 2013. The neonatal encephalopathy rate, fetal blood sampling rate, and the total number of cesarean and vaginal instrumental deliveries also decreased., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study examined the developmental trajectories of general and breathing movements in fetal twins. Fetal movement patterns were assessed from real-time ultrasound recordings performed at 12-15, 20-23, and 28-32 weeks of gestation in 42 twin pairs. Results indicated that both general movements and breathing movements followed a curvilinear, inverted U-shaped curve. Developmental trajectories were unrelated within pairs of twins and were not associated with gestational age at birth and birth weight. However, sex differences were found for general movements with males displaying more time making general movements at 21 weeks and a steeper decline in time spent making general movements during the second half of pregnancy than females. These age-related changes in fetal movements may reflect CNS development. These findings also suggest that twins' behavioral development is largely independent of co-twin development, gestational age at birth, and birth weight, but not of fetal sex., (© 2019 Wiley Periodicals, Inc.)

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.

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.)

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.

Objective: To study the effects of the tocolytics atosiban and ritodrine in term labour., Study Design: Women in term labour, requiring acute tocolysis, were prospectively randomized for treatment with either atosiban i.v. (n=70) or ritodrine i.v. (n=70). There were three indications for acute tocolysis: (1) fetal distress followed by continuation of labour, (2) fetal distress followed by emergency caesarean section (CS), and (3) arrest of contractions in women waiting for a secondary CS in the absence of fetal distress. Primary endpoints were maternal blood pressure (MBP) and maternal heart rate (MHR). Secondary endpoints were intra-uterine pressure, fetal heart rate (FHR), 5'-Apgar score and umbilical arterial pH., Results: Baseline characteristics did not differ between the study groups. The ritodrine group showed a significant rise in MHR (p<0.001), MHR remained unaltered in the atosiban group (p=0.31). No significant changes occurred in systolic and diastolic BP in either group. FHR rose by a maximum of 11.6 bpm (8.5%) in the ritodrine group (p<0.001) compared to a rise of 4.9 bpm (4.8%) in the atosiban group (p=0.27). No differences were found in blood loss and fetal outcome. Compared to baseline, uterine pressure was reduced by a maximum of 55% (p<0.001) after ritodrine administration, compared to a maximal reduction of 54% (p<0.001) after atosiban administration. These effects did not differ between the two treatment groups., Conclusion: Considering the maternal effects, our results suggest a possible role for atosiban bolus in acute tocolysis in term labour.