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Funder: British Heart Foundation; Id: http://dx.doi.org/10.13039/501100000274, Adopting an integrative approach, by combining studies of cardiovascular function with those at cellular and molecular levels, this study investigated whether maternal treatment with melatonin protects against programmed cardiovascular dysfunction in the offspring using an established rodent model of hypoxic pregnancy. Wistar rats were divided into normoxic (N) or hypoxic (H, 10% O2) pregnancy ± melatonin (M) treatment (5 μg·ml−1.day−1) in the maternal drinking water. Hypoxia ± melatonin treatment was from day 15–20 of gestation (term is ca. 22 days). To control for possible effects of maternal hypoxia‐induced reductions in maternal food intake, additional dams underwent pregnancy under normoxic conditions but were pair‐fed (PF) to the daily amount consumed by hypoxic dams from day 15 of gestation. In one cohort of animals from each experimental group (N, NM, H, HM, PF, PFM), measurements were made at the end of gestation. In another, following delivery of the offspring, investigations were made at adulthood. In both fetal and adult offspring, fixed aorta and hearts were studied stereologically and frozen hearts were processed for molecular studies. In adult offspring, mesenteric vessels were isolated and vascular reactivity determined by in‐vitro wire myography. Melatonin treatment during normoxic, hypoxic or pair‐fed pregnancy elevated circulating plasma melatonin in the pregnant dam and fetus. Relative to normoxic pregnancy, hypoxic pregnancy increased fetal haematocrit, promoted asymmetric fetal growth restriction and resulted in accelerated postnatal catch‐up growth. Whilst fetal offspring of hypoxic pregnancy showed aortic wall thickening, adult offspring of hypoxic pregnancy showed dilated cardiomyopathy. Similarly, whilst cardiac protein expression of eNOS was downregulated in the fetal heart, eNOS protein expression was elevated in the heart of adult offspring of hypoxic pregnancy. Adult offspring of hypoxic pregnancy further showed enhanced mesenteric vasoconstrictor reactivity to phenylephrine and the thromboxane mimetic U46619. The effects of hypoxic pregnancy on cardiovascular remodelling and function in the fetal and adult offspring were independent of hypoxia‐induced reductions in maternal food intake. Conversely, the effects of hypoxic pregnancy on fetal and postanal growth were similar in pair‐fed pregnancies. Whilst maternal treatment of normoxic or pair‐fed pregnancies with melatonin on the offspring cardiovascular system was unremarkable, treatment of hypoxic pregnancies with melatonin in doses lower than those recommended for overcoming jet lag in humans enhanced fetal cardiac eNOS expression and prevented all alterations in cardiovascular structure and function in fetal and adult offspring. Therefore, the data support that melatonin is a potential therapeutic target for clinical intervention against developmental origins of cardiovascular dysfunction in pregnancy complicated by chronic fetal hypoxia.

The effects of birth weight (BiW; low BiW [LBW] vs. high BiW [HBW]) and estimated breeding value (EBV) for protein deposition (low EBV [LBV] vs. high EBV [HBV]) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in growing pigs were studied. At an age of 14 wk, 10 LBW–LBV (BiW: 1.07 ± 0.09 [SD] kg; EBV: −2.52 ± 3.97 g/d, compared with an average crossbred pig with a protein deposition of 165 g/d), 10 LBW–HBV (BiW: 1.02 ± 0.13 kg; EBV: 10.47 ± 4.26 g/d), 10 HBW–LBV (BiW: 1.80 ± 0.13 kg; EBV: −2.15 ± 2.28 g/d), and 10 HBW–HBV (BiW: 1.80 ± 0.15 kg; EBV: 11.18 ± 3.68 g/d) male growing pigs were allotted to the experiment. The pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d dietary adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design. Pigs were fed 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention (in g/d) was higher in the HBW than in the LBW pigs (P < 0.001). The N retention (in g/[kg metabolic body weight (BW0.75) · d]) and N efficiency, however, were not affected by the BiW of the pigs. The N retention (P = 0.04) and N efficiency (P = 0.04) were higher in HBV than in LVB pigs on the A regime but were not affected by EBV in pigs on the R regime. Restricting the dietary protein supply with 30% decreased the N retention (P < 0.001) but increased the N efficiency (P = 0.003). Nontargeted metabolomics showed that a hexose, free amino acids (AA), and lysophosphatidylcholines were the most important metabolites in plasma for the discrimination between HBV and LBV pigs, whereas metabolites of microbial origin contributed to the discrimination between HBV and LBV pigs in urine. This study shows that BiW does not affect N efficiency in the later life of pigs. Nitrogen efficiency and N retention were higher in HBV than in LBV pigs on the A regime but similar in HBV and LBV pigs on the R regime. In precision feeding concepts aiming to further optimize protein and AA efficiency in pigs, the variation in EBV for protein deposition of pigs should be considered as a factor determining N retention, growth performance, and N efficiency.

International audience; Extensive epidemiological and experimental evidence have shown that exposure to an adverse intrauterine environment as observed in offspring of pregnancies complicated by obesity or diabetes, can program susceptibility to metabolic, endocrine and cardiovascular disorders later in life. Although most studies have concentrated on the maternal environment, it is also becoming evident that paternal exposure to obesity or diabetes can result in the later development of metabolic disorders in the offspring. Such programmed effects might not be limited to the first directly exposed generation, but could be transmitted to subsequent generations. This suggests the existence of mechanisms by which metabolic changes in parental phenotype are transmissible to offspring. The mechanisms which underpin the transmission of the programmed effects across generations are still unclear. However, epigenetic regulation of transcription has emerged as a strong candidate for mediating the heritability of metabolic diseases. Here, we review the most relevant evidence from human and animal studies showing transmission of programming effects of obesity or diabetes across generations, and the current mechanisms underlying either maternal or paternal influences on the metabolic status of offspring.

BACKGROUND: Maternal factors, including increasing childbearing age and various life-style factors, are associated with poorer short- and long-term outcomes for children, whereas knowledge of paternal parameters is limited. Recently, increasing paternal age has been associated with adverse obstetric outcomes, birth defects, autism spectrum disorders and schizophrenia in children. OBJECTIVE AND RATIONALE: The aim of this systematic review is to describe the influence of paternal factors on adverse short- and long-term child outcomes. SEARCH METHODS: PubMed, Embase and Cochrane databases up to January 2017 were searched. Paternal factors examined included paternal age and life-style factors such as body mass index (BMI), adiposity and cigarette smoking. The outcome variables assessed were short-term outcomes such as preterm birth, low birth weight, small for gestational age (SGA), stillbirth, birth defects and chromosomal anomalies. Long-term outcome variables included mortality, cancers, psychiatric diseases/disorders and metabolic diseases. The systematic review follows PRISMA guidelines. Relevant meta-analyses were performed. OUTCOMES: The search included 14 371 articles out of which 238 met the inclusion criteria, and 81 were included in quantitative synthesis (meta-analyses). Paternal age and paternal life-style factors have an association with adverse outcome in offspring. This is particularly evident for psychiatric disorders such as autism, autism spectrum disorders and schizophrenia, but an association is also found with stillbirth, any birth defects, orofacial clefts and trisomy 21. Paternal height, but not BMI, is associated with birth weight in offspring while paternal BMI is associated with BMI, weight and/or body fat in childhood. Paternal smoking is found to be associated with an increase in SGA, birth defects such as congenital heart defects, and orofacial clefts, cancers, brain tumours and acute lymphoblastic leukaemia. These associations are significant although moderate in size, with most pooled estimates between 1.05 and 1.5, and none exceeding 2.0. WIDER IMPLICATIONS: Although the increased risks of adverse outcome in offspring associated with paternal factors and identified in this report represent serious health effects, the magnitude of these effects seems modest.

Decisions about the use of psychotropic medication in pregnancy are an ongoing challenge for clinicians and women with mental health problems, owing to the uncertainties around risks of the illness itself to mother and fetus/infant, effectiveness of medications in pregnancy and risks to the fetus/infant from in utero exposure or via breast milk. These consensus guidelines aim to provide pragmatic advice regarding these issues. They are divided into sections on risks of untreated illness in pregnancy; general principles of using drugs in the perinatal period; benefits and harms associated with individual drugs; and recommendations for the management of specific disorders.

The major rate-limiting step in in vitro fertilization (IVF) success appears to be the implantation of the semi-allogeneic embryo into the maternal endometrium. To determine possible risk factors of recurrent failure of embryos to implant, we investigated immunogenetic determinants as level of human leukocyte antigen (HLA) histocompatibility, frequency of killer-cell immunoglobulin-like receptors (KIR) and HLA-C alleles and HLA-G polymorphism. We DNA typed women with recurrent implantation failure (RIF) and their partners for classical HLA Class I, HLA Class II, HLA-G and KIR alleles and compared these results with couples with successful embryo implantation after their first IVF and normal fertile couples. No association was found between RIF and the degree of histocompatibility between partners or sharing of a specific antigen. Also, no significant difference in KIR haplotype or combination of HLA-C group and KIR was observed. We did find a higher frequency of HLA-C2 and a higher frequency of 14base pair (bp) insertion in HLA-G in women with RIF. Therefore we conclude that the degree of histocompatibility between partners is not a determining factor for the occurrence of RIF. However, presence of the HLA-C2 allotype and the HLA-G allele with a 14bp insertion is a significant risk factor.

Europe has the highest proportion of elderly people in the world. Cardiovascular disease, type 2 diabetes, sarcopenia and cognitive decline frequently coexist in the same aged individual, sharing common early risk factors and being mutually reinforcing. Among conditions which may contribute to establish early risk factors, this review focuses on maternal obesity, since the epidemic of obesity involves an ever growing number of women of reproductive age and children, calling for appropriate studies to understand the consequences of maternal obesity on the offspring's health and for developing effective measures and policies to improve people's health before their conception and birth. Though the current knowledge suggests that the long-term impact of maternal obesity on the offspring's health may be substantial, the outcomes of maternal obesity over the lifespan have not been quantified, and the molecular changes induced by maternal obesity remain poorly characterized. We hypothesize that maternal insulin resistance and reduced placental glucocorticoid catabolism, leading to oxidative stress, may damage the DNA, either in its structure (telomere shortening) or in its function (via epigenetic changes), resulting in altered gene expression/repair, disease during life, and pathological ageing. This review illustrates the background to the EU-FP7-HEALTH-DORIAN project. © 2014 S. Karger GmbH, Freiburg.

This work assesses the urinary metabolite signature of prematurity in newborns by nuclear magnetic resonance (NMR) spectroscopy, while establishing the role of possible confounders and signature specificity, through comparison to other disorders. Gender and delivery mode are shown to impact importantly on newborn urine composition, their analysis pointing out at specific metabolite variations requiring consideration in unmatched subject groups. Premature newborns are, however, characterized by a stronger signature of varying metabolites, suggestive of disturbances in nucleotide metabolism, lung surfactants biosynthesis and renal function, along with enhancement of tricarboxylic acid (TCA) cycle activity, fatty acids oxidation, and oxidative stress. Comparison with other abnormal conditions (respiratory depression episode, large for gestational age, malformations, jaundice and premature rupture of membranes) reveals that such signature seems to be largely specific of preterm newborns, showing that NMR metabolomics can retrieve particular disorder effects, as well as general stress effects. These results provide valuable novel information on the metabolic impact of prematurity, contributing to the better understanding of its effects on the newborn's state of health. info:eu-repo/semantics/publishedVersion

Our aim was to determine functional outcome of very preterm-born and small-for-gestational-age (SGA) children as compared with matched controls at school age.We included 28 very preterm SGA children (GA32 wk, birth weight (BW)10th percentile), born in 2000-2001. We also included 28 very preterm but appropriate-for-gestational-age (AGA) children, matched for GA, gender, and birth year, as controls. We assessed motor skills, intelligence quotient (IQ), attention, verbal memory, visual perception, visuomotor integration, executive functioning, and behavior of both sets of children at school age.The SGA children had a median GA of 29.7 wk and BW of 888 g, whereas the controls had a median GA of 29.4 wk and BW of 1,163 g. At 8.6 y, the median total IQ of the SGA children was 94 as compared with 95 in the controls (not significant). Performance IQ was significantly lower in SGA children (89 vs. 95, P = 0.043), whereas verbal IQ was not (95 vs. 95). Total motor skills (P = 0.048) and fine motor skills (P = 0.021) were worse in SGA children. Furthermore, SGA children scored lower on selective attention (P = 0.026) and visual perception (P = 0.025). Other scores did not differ significantly between groups.The differences we found between the groups were small. This suggests that the impaired functioning of very preterm-born SGA children is attributable to their having been born very preterm rather than to being SGA.

Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later.The hypothesis that epigenetic mechanisms may link such nutritional imbalances with altered disease risk has been gaining acceptance over recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic marks include DNA methylation, histone modifications and a variety of non-coding RNAs. Strikingly, they are plastic and respond to environmental signals, including diet. Here we will review how dietary factors modulate the establishment and maintenance of epigenetic marks, thereby influencing gene expression and, hence, disease risk and health. (C) 2012 Elsevier Masson SAS. All rights reserved.

In pig production, within-batch variation in body weight (BW) gain of piglets during the nursery period (up to 10 weeks of age) can be high and is of high economic importance. Homogeneity of BW within batches of animals is important as it influences the efficiency of use of the grower and finisher facilities, and provides an extra value for the fattening farms. In the current study, factors for a low BW at the end of the nursery period of pigs were determined by analysing datasets from three different Swine Research Centres in the Netherlands and France. The entire dataset contained information on 77,868 individual piglets born in the period between 2005 and 2010. BW was determined at different time points over the pre- and post-weaning phase, and sex, season of birth; litter information (litter size at day of birth and after cross-fostering, number of piglets born alive per litter, number of total born littermates, sow parity number); cross-fostered animals (yes or no), and pen group size over the post-weaning period were recorded. A risk factor analysis approach was used to analyze the datasets to determine factors that predict piglet BW at the end of the nursery period. BW at the end of the nursery period corrected for age was mainly determined by season (P 0.05) contribute to explaining the BW at the end of the nursery period. To discard the possibility of intrauterine growth retarded piglets (IUGR) being the reason for the influence of birth weight (BiW) as an explanatory factor in the regression model, a further analysis was performed on the effect of this category of piglets on the results of the regression analysis. Overall, it was concluded that piglet's BW at the end of the nursery phase is mainly determined by season, sex, birth and weaning weight and BW at 6 weeks of age. Piglets with a BiW higher than the mean BiW minus 2.5 times the SD have the potential to compensate during the subsequent phases of growth.

The diet of the mother during pregnancy influences the onset of different diseases and health-related traits in the offspring. We investigated the influence of the mother hen diet on the intestinal gene expression pattern in the offspring. Hens received for 11 weeks either a commercial feed or a commercial feed supplemented with vitamins and minerals. The offspring of the two groups showed no changes in growth rate or feed conversion. Of this offspring, gene expression patterns in the intestine were measured at 3 and 14 days of age with an intestinal eDNA-microarray. Between the two groups, 11 genes were found to be differentially expressed both at 3 and 14 days of age. Thus, these genes were differently regulated when the intestine is developing as well as when the intestine is more mature. Genes that are differentially expressed at day 3 and/or day 14 affect intestinal turnover, proliferation and development, metabolism and feed absorption. To confirm that differences in gene expression are related to intestinal development, we investigated intestinal proliferation. This indeed also showed differences in proliferation between the two groups at day 3 and day 14 of age. The gene expression and proliferation results indicate that feed of the hens influences the functionality of intestine of the offspring at day 3 and 14 of age. (c) 2006 Elsevier Inc. All rights reserved.

The 'classical' concept that pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) primarily originate from defective placentation in early pregnancy has been challenged recently. There is growing evidence that other factors, including maternal predisposing conditions, also play a significant role in the pathophysiology of PIH and PE. The aim of the present study was to test the hypothesis that PIH and PE with an early onset and poor pregnancy outcome is associated with defective placentation, e.g. inadequate spiral artery dilatation and subsequent reduced uteroplacental perfusion, whereas PIH and PE with normal pregnancy outcome is not. Using Doppler ultrasound, we measured the uterine artery pulsatility index (PI) in a population of 531 nulliparous women in the 22nd week of gestation. Uterine artery PI was used as an index of resistance to blood flow in the uteroplacental circulation. Outcome measures were PIH/PE with or without poor pregnancy outcome, preterm birth and intra-uterine growth restriction (IUGR). The results revealed a striking difference between PI values for PIH/PE with and without poor pregnancy outcome. Uterine artery PI in the 22nd week was increased significantly in pregnancies which developed early-onset (before 35 weeks) PIH/PE with a poor pregnancy outcome. in contrast, uterine artery PI values were normal in women who developed PIH/PE, but had a good pregnancy outcome. There was a significant correlation between 22nd week uterine artery PI and subsequent preterm birth or IUGR. Our results indicate that only PIH/PE with poor pregnancy outcome is associated with defective placentation, whereas PIH/PE with good outcome is not. These findings support the concept of heterogeneous causes of hypertensive disorders of pregnancy.

Although there is substantial evidence that preeclampsia has a genetic background, the complexity of the processes involved and the fact that preeclampsia is a maternal-fetal phenomenon does not make the search for the molecular basis of preeclampsia genes easy. It is possible that the single phenotype 'preeclampsia' in fact should be divided into different sub-groups on genetic or biochemical level. In the present review, the preeclampsia phenotype and its pathophysiologic features are discussed. Family studies and postulated inheritance models are summarized. A systematic overview is given on the numerous candidate gene studies and gene-expression studies performed so far and on the currently available genome-wide scan data. Despite extensive research the molecular genetic basis of preeclampsia remains unclear. Future studies will hopefully enhance our insights in the molecular pathogenesis of preeclampsia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

The major rate-limiting step in in vitro fertilization (IVF) success appears to be the implantation of the semi-allogeneic embryo into the maternal endometrium. To determine possible risk factors of recurrent failure of embryos to implant, we investigated immunogenetic determinants as level of human leukocyte antigen (HLA) histocompatibility, frequency of killer-cell immunoglobulin-like receptors (KIR) and HLA-C alleles and HLA-G polymorphism. We DNA typed women with recurrent implantation failure (RIF) and their partners for classical HLA Class I, HLA Class II, HLA-G and KIR alleles and compared these results with couples with successful embryo implantation after their first IVF and normal fertile couples. No association was found between RIF and the degree of histocompatibility between partners or sharing of a specific antigen. Also, no significant difference in KIR haplotype or combination of HLA-C group and KIR was observed. We did find a higher frequency of HLA-C2 and a higher frequency of 14base pair (bp) insertion in HLA-G in women with RIF. Therefore we conclude that the degree of histocompatibility between partners is not a determining factor for the occurrence of RIF. However, presence of the HLA-C2 allotype and the HLA-G allele with a 14bp insertion is a significant risk factor.

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes.We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia. (C) 2001 Harcourt Publishers Ltd.

Objective To investigate a new method of quantification of the diastolic notch of the flow velocity waveforms of uterine arteries in the prediction of hypertensive disorders of pregnancy.Methods Pulsed-wave Doppler was used to obtain flow velocity waveforms (FVWs) from the uterine arteries at 21-22 weeks of gestation from 531 nulliparous women and 94 multiparous women at high risk. From the FVWs, both the pulsatility index (PI) and the notch index (NI) were calculated and the predictive values for both indices were compared using logistic regression analysis for mild and severe early onset hypertensive pregnancy complications.Results Both the PI and the NI were poor predictors for mild gestational hypertension and pre-eclampsia; predictive values for severe early onset disease, however, were much better Logistic regression analysis showed the NI has no additional value compared with the Pf in the prediction of either mild or severe disease.Conclusions The NI offers the possibility to quantify the diastolic notch in uterine artery analysis. Compared to the PI, this does not lead to better predictive values for hypertensive disorders of pregnancy.

Objective: To assess the role of Doppler uterine artery screening in the prediction of recurring hypertensive disorders in a high-risk population.Methods: Ninety-four women with a history of hypertensive disorders in previous pregnancies underwent ultrasound color Doppler to analyze blood flow in the uterine arteries at 21-22 weeks of gestation. We evaluated the performance of the Pulsatility Index (PI) as well as the diastolic notch to predict recurring hypertensive disorders. Outcome measures were the recurrence of hypertensive disorders, and poor pregnancy outcome due to intrauterine death growth retardation, intrauterine death, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, eclampsia, or premature birth. Onset of symptoms was before 35 weeks in all cases of poor pregnancy outcome.Results: Doppler flow recordings were obtained from a well-defined location in both uterine arteries. The predictive value of the uterine artery PI for recurring hypertensive disease was poor and not significant; interestingly, however, the predictive values for poor pregnancy outcome were good (sensitivity 83%, specificity 71%, p Conclusions: Uterine artery screening did significantly predict the recurrence of poor pregnancy outcome due to hypertensive complications in this high-risk group. In contrast, gestational hypertension and preeclampsia with normal pregnancy outcome were not significantly predicted by uterine artery screening.

Frisbie, Forbes, and Pullum (1996) show that it is meaningful to account for low birth weight, preterm delivery, and intrauterine growth-retardation when analyzing differences in compromised birth outcomes and infant mortality among racial and ethnic groups. I compare their findings for the 1987 U.S. birth cohort with findings for the 1988 U.S. birth cohort, using linked birth and infant death vital statistics from the National Center for Health Statistics. I focus on their calculation of fetal growth curves, which are highly at odds with the curves commonly used in the obstetric and pediatric literature. I compare birth outcome distributions and infant death probabilities using Frisbie et al.'s method and other standards. I conclude that Frisbie et al.'s method is not suited for the study of intrauterine growth-retardation at the population level because of the major flaws in gestational age measurement that exist in the type of data they use. An appropriate alternative is to apply a standard of normal intrauterine growth derived from antenatal estimation of fetal weight-for-gestational-age to the vital statistics data.

To determine whether the use of video display terminals (VDTs) is associated with an increased risk of reduced birthweight (RBW) and preterm birth, a cohort of telephone operators who used VDTs at work was compared to a cohort of non-VDT-users. Among 2,430 women interviewed, 713 eligible singleton live births were reported. Exposure was estimated from company records and a representative sample of electromagnetic fields was measured at the VDT workstations, For RBW (less than or equal to 2,800 g), we found no excess risk associated with any VDT use during pregnancy (ends ratio [OR] = 0.9; 95% confidence interval [CI] = 0.5-1.7). For preterm birth (less than or equal to 37 weeks), we similarly found no excess risk (OR = 0.7: 95% CI = 0.4-1.1). The risks estimated did not change substantially when hours working with VDTs were used as exposure variables. By contrast, increased risks were found for several known risk factors for LBW and preterm birth. We conclude thar occupational VDT use does not increase the risk of RBW and preterm birth. (C) 1997 Wiley-Liss, Inc.

The developmental course of the quantitative aspects of early spontaneous motility was studied longitudinally in fourteen intrauterine growth-retarded infants, with a birth weight below the 5th percentile, in relation to perinatal variables, brain ultrasound findings and neurological outcome. Quantitative motility was studied during the preterm period until term age, from 1 h videotape recordings, using Prechtl's classification of different spontaneous movement patterns. Comparison to a low-risk reference group, consisting of preterm, appropriate-for-gestational age infants, showed that significant differences were inconsistent and obviously by chance, with the possible exception of a decreased rate of startles from the 2nd to the 6th postnatal weeks. A trend of increasing duration of GMs was present with increasing postnatal age. There were hardly any correlations between perinatal variables and quantitative motility, and if present the correlations were weak. Such correlations were found between the reduction of heart-rate variability on cardiotocography and the rate of startles and twitches during the first week and furthermore between the neonatal blood glucose level and the rate of isolated arm movements and total motility during the first week. This study demonstrates that intrauterine growth retardation has little or no influence on the quantitative aspects of spontaneous motility postnatally during the preterm period. (C) 1997 Elsevier Science Ireland Ltd.

In order to document in detail the developmental course of qualitative aspects of early spontaneous motility in intrauterine growth-retarded infants, sequential videotape recordings were made in 19 preterm infants with a birth weight below the 5th percentile. The quality of general movements (GMs) was studied longitudinally during the preterm and postterm period until approximately 20 weeks corrected age, using Prechtl's method of quality assessment. An abnormal quality of GMs was present in 15 out of 19 infants. Compared to a low-risk group, consisting of appropriate-for-gestational age preterm infants, the proportion of infants with normal findings on brain scans who had an abnormal quality of GMs was high. The presence of 'abrupt chaotic' GMs was related to late fetal heart-rate decelerations and ischaemic alterations of the placenta. The quality of GMs normalized before or during the third month postterm in most infants with abnormal GMs. In four infants, the GMs did not normalize during the study period. The quality of fidgety movements was, in particular, a marker for neurological outcome at 24 months. This study demonstrates that intrauterine growth retardation may cause prolonged, but in most cases transient brain dysfunction; the qualitative assessment of GMs may help to identify infants at increased risk for neurodevelopmental abnormalities. (C) 1997 Elsevier Science Ireland Ltd.

Increasing litter size has long been a goal of pig breeders and producers, and may have implications for pig (Sus scrofa domesticus) welfare. This paper reviews the scientific evidence on biological factors affecting sow and piglet welfare in relation to large litter size. It is concluded that, in a number of ways, large litter size is a risk factor for decreased animal welfare in pig production. Increased litter size is associated with increased piglet mortality, which is likely to be associated with significant negative animal welfare impacts. In surviving piglets, many of the causes of mortality can also occur in non-lethal forms that cause suffering. Intense teat competition may increase the likelihood that some piglets do not gain adequate access to milk, causing starvation in the short term and possibly long-term detriments to health. Also, increased litter size leads to more piglets with low birth weight which is associated with a variety of negative long-term effects. Finally, increased production pressure placed on sows bearing large litters may produce health and welfare concerns for the sow. However, possible biological approaches to mitigating health and welfare issues associated with large litters are being implemented. An important mitigation strategy is genetic selection encompassing traits that promote piglet survival, vitality and growth. Sow nutrition and the minimisation of stress during gestation could also contribute to improving outcomes in terms of piglet welfare. Awareness of the possible negative welfare consequences of large litter size in pigs should lead to further active measures being taken to mitigate the mentioned effects.

Dietary glutamate is extensively oxidized in enterocytes during its trans-cellular journey from the intestinal lumen to the blood. This corresponds to high energy requirement for the absorptive function and renewal of the epithelium. Excitatory amino acid carrier 1 (EAAC1) is known to be the major transporter of glutamate in the intestine. The present study was conducted in Huanjiang mini-piglets which represent a valuable agronomical model for pig production and also extrapolation to human intestinal physiology in order: (i) to determine the amino acid sequence of EAAC1; (ii) to measure the ontogenic expression profiles of jejunal EAAC1 during the suckling period and (iii) to evaluate the influence of low body weight at birth on the expression of EAAC1. For such a purpose, we cloned EAAC1 from Huanjiang mini-pig and used real-time RT-PCR method and Western blotting analysis. Our results show that EAAC1 in the mini-pig encoded a predicted 524-AA protein with eight putative trans-membrane domains. The expression in mRNA and protein of EAAC1 in jejunum was increasing from birth up to 14 days of age and then decreased at 21 days. Piglets with small BW had lower jejunal EAAC1 protein content between birth and after 7 days suckling. These findings indicate that the expression of the EAAC1 in jejunum is much depending on the stage of piglet development and that low BW at birth is associated with lower expression of this carrier in the early suckling period. Then, it can be hypothesized that lower expression of the intestinal glutamate carrier may decrease the availability of glutamate to enterocytes, thus challenging the optimal absorptive function of the small intestine and normal mucosal growth.

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration of greater than or equal to 2 . 0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2 . 9 per cent) in the control group (P=NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level of greater than or equal to 2 . 0 MOM, compared with five in the control group (7 . 1 per cent; P=0 . 0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P=0 . 0042; relative risk=2 .). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from a dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.

Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later. The hypothesis that epigenetic mechanisms may link such nutritional imbalances with altered disease risk has been gaining acceptance over recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic marks include DNA methylation, histone modifications and a variety of non-coding RNAs. Strikingly, they are plastic and respond to environmental signals, including diet. Here we will review how dietary factors modulate the establishment and maintenance of epigenetic marks, thereby influencing gene expression and, hence, disease risk and health. (C) 2012 Elsevier Masson SAS. All rights reserved.

In pig production, within-batch variation in body weight (BW) gain of piglets during the nursery period (up to 10 weeks of age) can be high and is of high economic importance. Homogeneity of BW within batches of animals is important as it influences the efficiency of use of the grower and finisher facilities, and provides an extra value for the fattening farms. In the current study, factors for a low BW at the end of the nursery period of pigs were determined by analysing datasets from three different Swine Research Centres in the Netherlands and France. The entire dataset contained information on 77,868 individual piglets born in the period between 2005 and 2010. BW was determined at different time points over the pre- and post-weaning phase, and sex, season of birth; litter information (litter size at day of birth and after cross-fostering, number of piglets born alive per litter, number of total born littermates, sow parity number); cross-fostered animals (yes or no), and pen group size over the post-weaning period were recorded. A risk factor analysis approach was used to analyze the datasets to determine factors that predict piglet BW at the end of the nursery period. BW at the end of the nursery period corrected for age was mainly determined by season (P 0.05) contribute to explaining the BW at the end of the nursery period. To discard the possibility of intrauterine growth retarded piglets (IUGR) being the reason for the influence of birth weight (BiW) as an explanatory factor in the regression model, a further analysis was performed on the effect of this category of piglets on the results of the regression analysis. Overall, it was concluded that piglet's BW at the end of the nursery phase is mainly determined by season, sex, birth and weaning weight and BW at 6 weeks of age. Piglets with a BiW higher than the mean BiW minus 2.5 times the SD have the potential to compensate during the subsequent phases of growth.

The usefulness of the Rossavik growth model in predicting crown-heel length (CHL) was evaluated in 50 women with normal singleton pregnancies in a Dutch population. The femur diaphysis lengths (FDL) were predicted assuming growth cessation at 38, 39, 39.5, and 40 weeks, menstrual age (MA), and at birth using Rossavik growth models determined from two second-trimester FDL measurements. Predicted CHLs were then calculated from predicted FDLs using six different equations. Predicted CHLs were compared with the actual neonatal CHLs and the percent differences calculated. The growth potential realization index (GPRI) values were also determined.With all six equations, regression analysis revealed a significant relationship between the percent differences and birth ages for those infants delivering after 38 and 39 weeks, MA, respectively. The signs of the slopes of the regression lines were negative, indicating continued growth of these fetuses. With the Vintzileos equation, no evidence of continued growth was obtained after 39.5 weeks, MA. The systematic prediction error at this time point was 0.9%, whereas the random error was 3.3%. The mean GPRI(CHL) was 99%, with a 95% range of 93% to 104%. These findings indicate that the CHL can be predicted with a high degree of accuracy in this Dutch population if the appropriate growth cessation age and FDL-CHL function are used. (C) 1994 John Wiley and Sons, Inc.

OBJECTIVE: To examine the association between sucking patterns and the quality of fidgety movements in preterm infants. STUDY DESIGN: We studied the sucking patterns and fidgety movements of 44 preterm infants (gestational age 50 weeks) was correlated with the quality of fidgety movements (Spearman ρ = -0.33; P = .035). The percentage per infant of normal and uncoordinated sucking patterns was also correlated with the quality of fidgety movements (ρ = 0.31; P = .048 and ρ = -0.33; P = .032, respectively). Infants with uncoordinated sucking patterns had a higher rate of abnormal fidgety movements (OR, 7.5; 95% CI, 1.4-40; P = .019). CONCLUSION: The development of sucking patterns in preterm infants was related to the quality of fidgety movements. Uncoordinated sucking patterns were associated with abnormal fidgety movements, indicating that uncoordinated sucking, swallowing, and breathing may represent neurologic dysfunction.

OBJECTIVE: To compare functional outcomes of 7-year-old (school-age) children born small for gestational age (SGA; ie, a birth weight z score ≤ -1 SD), with appropriate for gestational age (AGA) peers, born moderately preterm or full term.STUDY DESIGN: Data were collected as part of the Longitudinal Preterm Outcome Project study, a community-based, prospective cohort study of 336 AGA and 42 SGA born children (median gestational age 35 weeks, range 31-41). Of the SGA children, 32 were moderately preterm, 10 were full term; of the AGA, these numbers were 216 and 120, respectively. At 6.9 years, we assessed intelligence, verbal memory, attention, visuomotor integration, and motor skills and we collected the parent-reported executive functioning. We compared the outcomes of the SGA children with those of their AGA peers.RESULTS: The performance of SGA children was similar to that of their AGA peers, except for attention control which was abnormal more often in SGA children (OR 3.99, 95% CI 1.32-12.12). The IQ of SGA children was 3 points lower, but this difference failed to reach significance.CONCLUSIONS: At school age, children born SGA have a greater risk of abnormal test scores on attention control than children born AGA, independent of gestational age. Their motor and many other cognitive functions are similar. The impact of these outcomes seems limited. Nevertheless, the consequences for school performance deserve attention.

INTRODUCTION: In neonates with spina bifida aperta (SBA), leg movements by myotomes caudal to the meningomyelocele (MMC) are transiently observed. It is unclear whether these leg movements relate to functional neural conduction through the MMC. For optimal therapeutical intervention, pathophysiological insight in these transient leg movements seems relevant. If leg movements by myotomes caudal to the MMC concur with the execution of general movements (GMs), functional neural conduction through the MMC is implicated.OBJECTIVE: In neonates with SBA, we aimed to determine whether the transiently present leg movements caudal to the MMC indicate functional neural conduction through the MMC.METHODS: During the perinatal period, fetuses and neonates with SBA (n = 7 and n = 13, respectively) were longitudinally analysed for concurrency between leg movements caudal to the MMC and GMs. To address the integrity of the reflex arc in spinal segments (at, or) caudal to the MMC, tendon leg reflexes were assessed during the first postnatal week.RESULTS: At postnatal day 1, leg movements caudal to the MMC concurred with GMs in 12 of 13 infants. Isolated leg movements were observed in only 3 of these 12 infants (isolated vs. concurrent; p < 0.005). Leg movements concurring with GMs lasted longer than isolated leg movements (median duration = 11 s vs. 2 s; p < 0.05). Between days 1 and 7, tendon leg reflexes (at, or) caudal to the MMC had disappeared in all but 1 neonate. However, leg movements caudal to the MMC remained concurrently present with GMs in all five neonates available for follow-up after day 7. Comparing these leg movements between days 1 and 7 indicated a decreased duration (-44%, p < 0.05).CONCLUSIONS: In neonates with SBA, leg movements caudal to the MMC concur with GMs, indicative of functional neural conduction through the MMC. The disappearance of these leg movements is caused by lower motor neuron dysfunction at the reflex arc, whereas neural conduction through the MMC is still functional.

Objective: To assess the relationship of energy stress during pregnancy and lactation to maternal body stores in marginally nourished rural Bangladeshi women. Subjects and methods: Two-hundred and fifty-two women were followed from 5 - 7 months of pregnancy until 6 months postpartum. Energy intake was estimated during pregnancy and at 1, 3 and 6 month(s) postpartum using 24 h dietary recall. Body weight was measured on enrollment, another once or twice during pregnancy, and at 1, 3 and 6 month(s) postpartum. The weekly rates of pregnancy weight gain and postpartum weight changes were determined. Weight and length of the infants were measured at birth and at approximately 1, 3 and 6 month(s). Results: Maternal energy intake at 5 - 7 months of gestation was 1464 +/- 416 kcal/day (mean s.d.). Women gained a mean of 200 g/week or a total of 4 kg during the second half of pregnancy. An analysis of maternal weight showed no indication of accrual of fat stores during pregnancy. Dietary energy during lactation exceeded the intake during pregnancy by 248 +/- 354 kcal/day. Mothers lost an estimated average of I kg of weight during the first 6 months of lactation. The mean ( s.d.) birth weight was 2.55 +/- 0.38 kg, and the prevalence of low birth weight (

Objective To investigate a new method of quantification of the diastolic notch of the flow velocity waveforms of uterine arteries in the prediction of hypertensive disorders of pregnancy. Methods Pulsed-wave Doppler was used to obtain flow velocity waveforms (FVWs) from the uterine arteries at 21-22 weeks of gestation from 531 nulliparous women and 94 multiparous women at high risk. From the FVWs, both the pulsatility index (PI) and the notch index (NI) were calculated and the predictive values for both indices were compared using logistic regression analysis for mild and severe early onset hypertensive pregnancy complications. Results Both the PI and the NI were poor predictors for mild gestational hypertension and pre-eclampsia; predictive values for severe early onset disease, however, were much better Logistic regression analysis showed the NI has no additional value compared with the Pf in the prediction of either mild or severe disease. Conclusions The NI offers the possibility to quantify the diastolic notch in uterine artery analysis. Compared to the PI, this does not lead to better predictive values for hypertensive disorders of pregnancy.

Objective: To assess the role of Doppler uterine artery screening in the prediction of recurring hypertensive disorders in a high-risk population. Methods: Ninety-four women with a history of hypertensive disorders in previous pregnancies underwent ultrasound color Doppler to analyze blood flow in the uterine arteries at 21-22 weeks of gestation. We evaluated the performance of the Pulsatility Index (PI) as well as the diastolic notch to predict recurring hypertensive disorders. Outcome measures were the recurrence of hypertensive disorders, and poor pregnancy outcome due to intrauterine death growth retardation, intrauterine death, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, eclampsia, or premature birth. Onset of symptoms was before 35 weeks in all cases of poor pregnancy outcome. Results: Doppler flow recordings were obtained from a well-defined location in both uterine arteries. The predictive value of the uterine artery PI for recurring hypertensive disease was poor and not significant; interestingly, however, the predictive values for poor pregnancy outcome were good (sensitivity 83%, specificity 71%, p

The developmental course of the quantitative aspects of early spontaneous motility was studied longitudinally in fourteen intrauterine growth-retarded infants, with a birth weight below the 5th percentile, in relation to perinatal variables, brain ultrasound findings and neurological outcome. Quantitative motility was studied during the preterm period until term age, from 1 h videotape recordings, using Prechtl's classification of different spontaneous movement patterns. Comparison to a low-risk reference group, consisting of preterm, appropriate-for-gestational age infants, showed that significant differences were inconsistent and obviously by chance, with the possible exception of a decreased rate of startles from the 2nd to the 6th postnatal weeks. A trend of increasing duration of GMs was present with increasing postnatal age. There were hardly any correlations between perinatal variables and quantitative motility, and if present the correlations were weak. Such correlations were found between the reduction of heart-rate variability on cardiotocography and the rate of startles and twitches during the first week and furthermore between the neonatal blood glucose level and the rate of isolated arm movements and total motility during the first week. This study demonstrates that intrauterine growth retardation has little or no influence on the quantitative aspects of spontaneous motility postnatally during the preterm period. (C) 1997 Elsevier Science Ireland Ltd.

In order to document in detail the developmental course of qualitative aspects of early spontaneous motility in intrauterine growth-retarded infants, sequential videotape recordings were made in 19 preterm infants with a birth weight below the 5th percentile. The quality of general movements (GMs) was studied longitudinally during the preterm and postterm period until approximately 20 weeks corrected age, using Prechtl's method of quality assessment. An abnormal quality of GMs was present in 15 out of 19 infants. Compared to a low-risk group, consisting of appropriate-for-gestational age preterm infants, the proportion of infants with normal findings on brain scans who had an abnormal quality of GMs was high. The presence of 'abrupt chaotic' GMs was related to late fetal heart-rate decelerations and ischaemic alterations of the placenta. The quality of GMs normalized before or during the third month postterm in most infants with abnormal GMs. In four infants, the GMs did not normalize during the study period. The quality of fidgety movements was, in particular, a marker for neurological outcome at 24 months. This study demonstrates that intrauterine growth retardation may cause prolonged, but in most cases transient brain dysfunction; the qualitative assessment of GMs may help to identify infants at increased risk for neurodevelopmental abnormalities. (C) 1997 Elsevier Science Ireland Ltd.

Objective To determine whether blood levels of atrial natriuretic peptide in small for gestational age (SGA) fetuses are related to Doppler indices measured in arterial and venous vessels. Methods Atrial natriuretic peptide was assayed in fetal blood obtained at funipuncture in 42 third-trimester fetuses, of whom 11 were appropriate for gestational age (AGA) and 31 were SGA. Small for gestational age fetuses were divided into three groups according to Doppler findings in the umbilical artery and inferior vena cava: 1) normal in both vessels (n = 10); 2) abnormal in the umbilical artery but normal in the inferior vena cava (n = 10); and 3) abnormal in both vessels (n = 11). Atrial natriuretic peptide levels were related to Doppler indices and acid-base status of the fetal blood. Results Small for gestational age fetuses with abnormal waveforms in both vessels had higher atrial natriuretic peptide blood levels (median 544.8 pg/mL, range 404.2–1112.3) compared with AGA fetuses (median 316.8 pg/mL, range 159.3–470.1; P ≤ .001), SGA fetuses with normal waveforms only in both vessels (median 299.8 pg/mL, range 242.6–480.5; P ≤ .001), and SGA fetuses with abnormal waveforms only in the umbilical artery (median 367.6 pg/mL, range 192.7–748.9; P = .002). Blood levels of atrial natriuretic peptide were significantly related to the preload index in the inferior vena cava (ρ = 0.554, P ≤ .001). This relation remained significant when the analysis was restricted to the SGA fetuses with abnormal waveforms in the umbilical artery and the inferior vena cava (ρ = 0.673, P = .03). Conclusions Small for gestational age fetuses with abnormal velocity waveforms in the inferior vena cava have significantly higher concentrations of atrial natriuretic peptide. This may represent a compensatory mechanism in the SGA fetus for regulation of an abnormal hemodynamic condition.

To determine whether the use of video display terminals (VDTs) is associated with an increased risk of reduced birthweight (RBW) and preterm birth, a cohort o f telephone operators who used VDTs at work was compared to a cohort of non- VDT- use rs. Am ong 2,430 women interviewed, 713 eligible singleton live births were reported. Exposure was estim ated from company records and a representative sample of electromagnetic fields was m easured at the VDT workstations. For RBW (^2,800 g)t we found no excess risk associated with any VDT use during pregnancy (odds ratio [OR] = 0.9; 95% confidence interval [C l] — 0.5—1,7). For preterm birth 37 weeks), we similarly found no excess risk (OR ~ 0.7; 95% C I = 0.4-1.1). The risks estimated did not change substantially when hours working with VDTs were used as exposure variables. By contrast, increased risks were found fo r several known risk factors fo r LBW and preterm birth. We conclude that occupational VDT use does not increase the risk o f RBW and preterm birth. Am. J. Ind. Med. 32:681-688, 1997. © 1997 Wiley-Liss, lnc.f

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration of greater than or equal to 2 . 0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2 . 9 per cent) in the control group (P=NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level of greater than or equal to 2 . 0 MOM, compared with five in the control group (7 . 1 per cent; P=0 . 0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P=0 . 0042; relative risk=2 .). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from a dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.

The possibility of studying fetal motor behaviour by ultrasound techniques has provoked research on its potential application for assessment of prenatal neurological conditions. The characteristics ('quality') of one particular movement pattern, the 'general movement', has been shown to be discriminative between uncomplicated pregnancy and major pathology of the developing central nervous system. Some recent studies have investigated whether the quality and/or the quantity of fetal movements correlated with other clinical variables during complicated pregnancies, and whether they provided prognostic information for the neurological outcome. Longitudinal research encompassing the pre- and postnatal periods was performed on uncomplicated pregnancies and on pregnancies complicated by intrauterine growth retardation, oligohydramnios (due to premature rupture of the amniotic membranes), or fetal breech position. Although the quantity of both fetal general movements and fetal breathing movements were found to be related to clinical variables of the fetal condition (such as heart rate variability, heart rate decelerations), clinical application seems limited due to large inter- and intra-individual variabilities. In contrast, the quality of fetal general movements appeared highly correlated with parameters of fetal clinical condition in individual cases and fulfilled several prerequisites for serving as a reliable diagnostic tool for prediction of the fetal condition and for assessment of the integrity of the central nervous system.

The possibility of studying fetal motor behaviour by ultrasound techniques has provoked research on its potential application for assessment of prenatal neurological conditions. The characteristics ('quality') of one particular movement pattern, the 'general movement', has been shown to be discriminative between uncomplicated pregnancy and major pathology of the developing central nervous system. Some recent studies have investigated whether the quality and/or the quantity of fetal movements correlated with other clinical variables during complicated pregnancies, and whether they provided prognostic information for the neurological outcome. Longitudinal research encompassing the pre- and postnatal periods was performed on uncomplicated pregnancies and on pregnancies complicated by intrauterine growth retardation, oligohydramnios (due to premature rupture of the amniotic membranes), or fetal breech position. Although the quantity of both fetal general movements and fetal breathing movements were found to be related to clinical variables of the fetal condition (such as heart rate variability, heart rate decelerations), clinical application seems limited due to large inter- and intra-individual variabilities. In contrast, the quality of fetal general movements appeared highly correlated with parameters of fetal clinical condition in individual cases and fulfilled several prerequisites for serving as a reliable diagnostic tool for prediction of the fetal condition and for assessment of the integrity of the central nervous system.