Significant reduction in umbilical artery metabolic acidosis after implementation of intrapartum ST waveform analysis of the fetal electrocardiogram.

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.

Using three-dimensional ultrasound in predicting complex gastroschisis: A longitudinal, prospective, multicenter cohort study.

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.

Developmental trajectories of general and breathing movements in fetal twins.

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.

Growth patterns in fetuses with isolated cardiac defects.

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.

Fetal behavior and heart rate in twin pregnancy: a review.

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.

New reference values for the neonatal cerebral ventricles.

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.

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study.

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.

Maternal body mass index does not affect performance of fetal electrocardiography.

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.

Reference curves for the normal fetal small bowel and colon diameters; their usefulness in fetuses with suspected dilated bowel.

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.

Adjustment to termination of pregnancy for fetal anomaly: a longitudinal study in women at 4, 8, and 16 months.

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.

Acute tocolysis for uterine activity reduction in term labor: a review.

This review critically evaluates the efficacy of different tocolytics in reducing uterine pressure and contractions in term labor. The available evidence supports the use of beta-adrenergic-receptor agonists such as terbutaline or ritodrine; they appear to have an immediate and comparable profound effect on uterine activity in term labor. However, the preferred type of beta-adrenergic receptor agonist and dosage are unclear. The oxytocin receptor antagonist atosiban has a high specificity for the uterus with limited or no systemic effects and could therefore be an attractive alternative for use in term labor. The evidence on the tocolytic potency of a single bolus of atosiban for tocolysis in term labor is encouraging but limited and needs further research. Moreover, atosiban lacks United States Food and Drug Administration approval. Literature documenting efficacy and safety of nitroglycerin or magnesium sulfate in term labor is far from convincing. The theoretical basis for the use of tocolytics for nonreassuring intrapartum fetal heart rate patterns is to reduce the aggravating influence of uterine contractions. However, the clinical evidence that tocolytics in term active labor are actually beneficial in improving neonatal outcome is very limited.

A prospective randomized trial of acute tocolysis in term labour with atosiban or ritodrine.

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.

Neonatal corticosteroid therapy affects growth patterns in early infancy.

OBJECTIVE: Although postnatal corticosteroid (CS) therapy has well established beneficial effects on pulmonary function, it may also result in growth restriction during treatment. The course of early childhood growth is believed to predict cardiovascular and metabolic diseases in adulthood. Therefore, we determined the effects of postnatal dexamethasone (DEX) or hydrocortisone (HC) treatment on patterns of postnatal growth until approximately four years of age. STUDY DESIGN: In an observational cohort study of children born prematurely (<32 weeks of gestation), we compared growth patterns for body weight, height, and head circumference from birth to age four years, of children who received DEX (boys: N = 30, girls: N = 14), HC (boys: N = 33, girls: N = 28) to a reference group that had not received postnatal CSs (boys: N = 52, girls: N = 53) using linear mixed-effects modeling. RESULTS: Growth velocity curves of CS-treated neonates showed a shift to the right, representing a delay in time. They had decreased absolute growth velocities during and shortly after treatment, followed by an increase in growth velocity thereafter. A shift to the right was also seen for the age at which maximal growth velocity of weight/height was reached in boys and girls. Fractional growth rates of weight, height, and head circumference were generally reduced in the CS-treated groups during the first two months of age, with catch-up growth in the following months. In DEX-treated infants these changes were more pronounced than in HC-treated infants. CONCLUSION: These data suggest that postnatal growth patterns of preterm born infants are affected by CS-treatment, more by DEX than by HC. Effects were observed mainly on growth velocities. This observation may have impact on health in later life for those individuals treated with CSs in the neonatal period. A definitive conclusion would require a randomized trial of these therapies.

Accuracy of diagnosis and counseling of fetal brain anomalies prior to 24 weeks of gestational age.

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.

Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial.

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: NCT00189007 Dutch Trial Register NTR1383.

Maternal decision to terminate pregnancy in case of Down syndrome.

OBJECTIVE: This study explores decisional processes regarding termination of pregnancy because of Down syndrome and aims to identify possibilities for improving counseling. STUDY DESIGN: Seventy-one women completed questionnaires 4 months after termination of pregnancy for Down syndrome, including motivations for the decision, reasons for doubt, perceived influence and/or pressure at decision-making, and satisfaction with the received health care. RESULTS: Child-related motivations to the termination were the most frequently mentioned, but almost all women indicated also motives of self-interest. Twenty-one percent of women reported much doubt. Perceived influence of the medical staff was substantial, but most women felt that they had not been put under pressure. Satisfaction with the caregivers was high. CONCLUSION: Women acknowledge that self-interested motives play an important role. Medical caregivers are among the most important persons for women who decide to terminate pregnancy because of Down syndrome.

Respiratory outcome in preterm small for gestational age fetuses with or without abnormal umbilical artery Doppler and/or maternal hypertension.

OBJECTIVE: To study respiratory outcome in preterm small for gestational age (SGA) fetuses with or without signs of intrauterine growth restriction due to placental insufficiency, and with or without maternal hypertension. METHODS: This was a retrospective study of 187 neonates with birth weight <10(th) percentile and gestational age <34 weeks. Results from umbilical artery Doppler velocimetry were used to identify the abnormal Doppler subgroup. RESULTS: No significant difference in respiratory outcome between SGA fetuses with normal (SGA-N) or abnormal (SGA-A) umbilical artery Doppler examination was found. Within the SGA-A group, the respiratory distress syndrome (RDS) incidence (OR 5.6, 95% CI 1.7-18.3), RDS grade (OR 6.7, 95% CI 1.2-38.5), and need for surfactant (OR 5.3, 95% CI 1.1-24.4) were higher in infants of women with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as compared to those of normotensive mothers. CONCLUSIONS: Lung maturation is not accelerated with placental insufficiency. SGA-A fetuses of mothers with HELLP syndrome have a significantly poorer respiratory outcome than those with healthy mothers. Possibly, fetuses of mothers with HELLP syndrome are subjected to 'oxidative stress' causing lung damage rather than lung maturation.

Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring.

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.

Does maternal prenatal stress adversely affect the child's learning and memory at age six?

Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50 boys, 62 girls, Age: M=6.7 years, SD=8.4 months), with the Test of Memory and Learning (TOMAL). Maternal stress levels were determined three times during pregnancy by self-report questionnaires. Furthermore, maternal saliva cortisol samples were used as a measure of hypothalamus-pituitary-adrenal axis functioning. Results of hierarchical multivariate regression analyses showed that maternal life events measured during the first part of pregnancy were negatively associated with the child's attention/concentration index, while controlling for overall IQ, gender, and postnatal stress. No associations were found between prenatal maternal cortisol and the offspring's learning and memory.

Lower birth weight and attenuated adrenocortical response to ACTH in offspring from sows that orally received cortisol during gestation.

Prenatal stress is known to affect several offspring characteristics, but its effects depend among other factors on the period of gestation in which it is applied. In the present study, oral administration of hydrocortisone-acetate (HCA) was used to elevate cortisol concentrations in pregnant sows to levels also observed after psychological stress. HCA was administered during three different periods of gestation (115 days in pigs): period 1: 21-50 (P1, n = 10), period 2: 51-80 (P2, n = 10) and period 3: 81-110 (P3, n = 10) days after insemination. Control sows (n = 11) received vehicle from 21-110 days after insemination. When P1-, P2- and P3-sows did not receive HCA, they also received vehicle. During gestation, weekly saliva samples were taken from the sows to determine salivary cortisol concentrations. Treatment effects on sow, litter and piglet characteristics were determined. In addition, two female piglets per litter were subjected to an ACTH-challenge test at 6 weeks of age to determine the adrenocortical response to ACTH. Pigs were slaughtered at 6 months of age and slaughter weight, back fat thickness and percentage of lean meat were analysed. During the period of treatment with HCA, salivary cortisol concentrations were increased in P1-, P2- and P3-sows compared to control sows (P < 0.01). The total number of piglets born per litter did not differ among treatment groups (P > 0.30), but pooled HCA-litters had a higher percentage of live born piglets (P < 0.05) and fewer mummies than control litters (P < 0.05). Gestation length did not differ among treatment groups (P = 0.21), but did affect treatment effects on birth weight. Overall, HCA-piglets weighed less at birth, and remained lighter until weaning (P < 0.05). The salivary cortisol concentrations after i.m. injection of ACTH (2.5 IU/kg) were lower in P1- and P3-piglets compared to control piglets. At slaughter, HCA-treatment indirectly decreased lean meat percentage and increased back fat thickness. In conclusion, elevated peripheral cortisol concentrations in pregnant sows affect both litter characteristics and piglet physiology, the latter depending on the period of gestation during which concentrations were elevated. Underlying mechanisms require further investigation.