Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction

Background: According to epidemiological studies, impaired intrauterine growth increases the risk for cardiovascular morbidity and mortality in adulthood. Heart rate variability (HRV), which reflects the autonomic nervous system function, has been used for risk assessment in adults while its dysfunction has been linked to poor cardiovascular outcome. Objective: We hypothesized that children who were born with fetal growth restriction (FGR) and antenatal blood flow redistribution have decreased HRV at early school age compared to their gestational age matched peers with normal intrauterine growth. Study design: A prospectively collected cohort of children born with FGR (birth weight = -2SD. Conclusions: Early school age children born with FGR and intrauterine blood flow redistribution demonstrated altered heart rate variability. These prenatal and postnatal findings may be helpful in targeting preventive cardiovascular measures in FGR.Peer reviewe

Fetal hemodynamics and language skills in primary school-aged children with fetal growth restriction : A longitudinal study

Aim: Long-term follow-up studies on children born with fetal growth restriction (FGR) have revealed a specific profile of neurocognitive difficulties, including problems with speech, language and literacy skills. We hypothesized that problems with communication skills, including language use and literacy skills of FGR children at primary school age are associated with prenatal circulatory changes. Methods: Ultrasonographic assessment of fetoplacental hemodynamics was performed prenatally in 77 fetuses. After a follow-up period of 8-10 years, assessment of reading and spelling skills using standardized tests and the Children's Communication Questionnaire (CCC-2) was performed to measure different language skills in 37 FGR children and 31 appropriately grown (AGA) controls, matched for gestational age. Results: Increased blood flow resistance in the umbilical artery (UA PI > 2 SD) during fetal life showed odds ratios of 3.5-19.1 for poor literacy and communication skills and need for speech and language therapy. Furthermore, FGR children with prenatal cerebral vasodilatation (cerebroplacental ratio (CPR) <-2 SD) had significantly poorer literacy and communication skills, at primary school age compared to the AGA controls. Abnormal CPR demonstrated odds ratios of 4.2-28.1 for poor literacy and communication skills and need for speech and language therapy. Conclusion: Increased blood flow resistance in the umbilical artery and cerebral vasodilatation are associated with poor communication, language, and literacy skills at early school age in children born with FGR. These findings indicate the need for continuous follow-up of this group and timely targeted support to ensure optimal academic outcomes.Peer reviewe

Means of reaching successful antenatal transfers to level 3 hospitals in cases of threatened very preterm deliveries: a national survey

Introduction Centralization of very preterm deliveries to level 3 hospitals is recommended to improve infant survival and prevent brain injury. We studied the clinical practices of centralization from level 2 to level 3 hospitals in cases of threatening very preterm delivery in Finland. Materials and methods Obstetricians in all 16 level 2 hospitals in Finland were invited to participate in an online survey regarding antenatal transfer to level 3 hospitals among women with threatened delivery below 32 gestational weeks. We report clinical thresholds used as indications and contraindications for antenatal transfers, and logistical factors related to transfers. Results Twelve out of 16 (75%) hospitals completed the survey. The lower gestational age threshold for antenatal transfer ranged from 22 + 0 to 23 + 0 weeks. All hospitals regarded preterm premature rupture of membranes, chorioamnionitis, and severe pre-eclampsia as indications for antenatal transfer to a level 3 hospital. Most hospitals reported transferring women in spite of regular contractions (interval over 5 min) or cervical dilatation up to 4 cm. Suspicion of placental abruption, abnormal cardiotocography tracing and poor maternal condition were the most frequently reported contraindications for antenatal transfer. The time to arrange antenatal transfer was less than 2 h in all hospitals, and overcrowding of level 3 hospitals rarely hindered antenatal transfer. Conclusions Successful centralization of very preterm deliveries is reached in Finland by rapid and active antenatal transfers. This study identified clinical thresholds used by obstetricians in a setting of long distances and high centralization rate.</div

Brain volumes and white matter microstructure in 8- to 10-year-old children born with fetal growth restriction

Background Fetal growth restriction caused by placental insufficiency is associated with increased risk of poor neurodevelopment, even in the absence of specific perinatal brain injury. Placental insufficiency leads to chronic hypoxaemia that may alter cerebral tissue organisation and maturation.Objective The aim of this study was to assess the effects fetal growth restriction and fetal haemodynamic abnormalities have on brain volumes and white matter microstructure at early school age.Materials and methods This study examined 32 children born with fetal growth restriction at 24 to 40 gestational weeks, and 27 gestational age-matched children, who were appropriate for gestational age. All children underwent magnetic resonance imaging (MRI) at the age of 8-10 years. Cerebral volumes were analysed, and tract-based spatial statistics and atlas-based analysis of white matter were performed on 17 children born with fetal growth restriction and 14 children with birth weight appropriate for gestational age.Results Children born with fetal growth restriction demonstrated smaller total intracranial volumes compared to children with normal fetal growth, whereas no significant differences in grey or white matter volumes were detected. On atlas-based analysis of white matter, children born with fetal growth restriction demonstrated higher mean and radial diffusivity values in large white matter tracts when compared to children with normal fetal growth.Conclusion Children ages 8-10 years old born with fetal growth restriction demonstrated significant changes in white matter microstructure compared to children who were appropriate for gestational age, even though no differences in grey and white matter volumes were detected. Poor fetal growth may impact white matter maturation and lead to neurodevelopmental impairment later in life.</p

Gestational anemia and maternal antenatal and postpartum psychological distress in a prospective FinnBrain Birth Cohort Study

BackgroundGestational anemia, most commonly caused by iron deficiency, may increase the risk of maternal anxiety and depression and have a potentially far-reaching impact on mother’s and newborn’s health. Several mechanisms, such as effects of iron deficiency on cerebral neurotransmitter metabolism, have been suggested. None of the earlier studies have assessed the association between gestational anemia and depression, anxiety and pregnancy-related anxiety simultaneously.MethodsWomen, participating in the FinnBrain Birth Cohort Study and attending maternity welfare clinics in Turku, whose hemoglobin (Hb) values during pregnancy were available were included in this study (n = 1273). The study group consisted of 301 women with Hb levels ResultsGestational anemia was not associated with an increased risk of depression either prenatally or postpartum when the analyses were adjusted for maternal age at birth, parity, smoking during pregnancy, maternal education, and gestational age. However, a weak connection was found between gestational anemia and prenatal anxiety in the early pregnancy. Furthermore, the analysis between women with Hb ConclusionsNo evidence supporting the association between gestational anemia and antenatal or postpartum depression was found. However, a weak connection between gestational anemia and antenatal anxiety was observed. This finding needs further investigation to establish timing and investigate causality.</p

Expression of CPPED1 in human trophoblasts is associated with timing of term birth

Understanding of timing of human parturition is incomplete. Therefore, we carried out proteomic analyses of full-term placentas from uncomplicated pregnancies to identify protein signatures associated with the onset of spontaneous delivery. We found quantitative associations of 10 proteins with spontaneous term birth, evident either in the basal or in the chorionic plates or in both. Additional 18 proteins were associated according to the location within placenta indicating local variations in protein amounts. Calcineurin-like phosphoesterase domain-containing 1 (CPPED1), a phosphatase previously suggested dephosphorylating AKT1/PKB, was one of the identified proteins. qRT-PCR revealed the mRNA level of CPPED1 was higher in elective caesarean deliveries than in spontaneous births, while immunohistochemistry showed CPPED1 in cytotrophoblasts, syncytiotrophoblasts and extravillous trophoblasts. Noteworthy, phosphorylation status of AKT1 did not differ between placentas from elective caesarean and spontaneous deliveries. Additionally, analyses of samples from infants indicated that single-nucleotide polymorphisms rs11643593 and rs8048866 of CPPED1 were associated with duration of term pregnancy. Finally, post-transcriptional silencing of CPPED1 in cultured HTR8/SVneo cells by siRNAs affected gene expression in pathways associated with inflammation and blood vessel development. We postulate that functions regulated by CPPED1 in trophoblasts at choriodecidual interphase have a role in the induction of term labour, but it may be independent of AKT1

Placental insufficiency and fetal heart: Doppler ultrasonographic and biochemical markers of fetal cardiac dysfunction

Abstract The first aim of this study was to investigate the relationship between Doppler ultrasonographic parameters and biochemical markers of human fetal cardiac dysfunction and myocardial cell damage in pregnancies complicated by placental insufficiency and/or fetal growth restriction. Our second aim was to examine fetal central and peripheral hemodynamic characteristics associated with retrograde aortic isthmus net blood flow. Fetuses with significant myocardial cell damage (cTnT > 0.10 ng/ml) had increased pulsatility in the blood velocity waveforms of ductus venosus, left hepatic vein and inferior vena cava, and had more often atrial pulsations in the umbilical vein. Their umbilical artery NT-proANP concentrations were higher than in fetuses without myocardial cell damage. The proportion of left ventricular cardiac output of the combined cardiac output was greater and the corresponding proportion of the right ventricle was less than in fetuses with only increased NT-proANP levels ( > 1145 pmol/l). Tricuspid regurgitation was present more often and the right ventricular fractional shortening was less in fetuses with myocardial cell damage than in fetuses with normal umbilical artery cTnT levels. In fetuses with placental insufficiency and/or growth restriction (n = 48), umbilical artery NT-proANP concentrations showed a significant positive correlation with ductus venosus, left hepatic vein and inferior vena cava pulsatility index values for veins. Fetuses with placental insufficiency and antegrade aortic isthmus net blood flow demonstrated a shift in their right ventricular cardiac output from the pulmonary to the systemic circulation, and foramen ovale volume blood flow made up the majority of the left ventricular cardiac output. Fetuses with retrograde aortic isthmus net blood flow failed to demonstrate these changes, and they had signs of increased left atrial pressure. In addition, right ventricular fractional shortening was decreased and the pulsatility in the ductus venosus blood velocity waveforms was increased. In conclusion, human fetal myocardial cell damage was associated with a rise in systemic venous pressure, a change in the distribution of cardiac output towards the left ventricle and a rise in right ventricular afterload. Fetuses with retrograde aortic isthmus net blood flow failed to rearrange the distribution of the cardiac output and they had signs of increased left atrial pressure. In addition, right ventricular afterload and pulsatility in the ductus venosus blood velocity waveforms were increased

Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction

Abstract Background: According to epidemiological studies, impaired intrauterine growth increases the risk for cardiovascular morbidity and mortality in adulthood. Heart rate variability (HRV), which reflects the autonomic nervous system function, has been used for risk assessment in adults while its dysfunction has been linked to poor cardiovascular outcome. Objective: We hypothesized that children who were born with fetal growth restriction (FGR) and antenatal blood flow redistribution have decreased HRV at early school age compared to their gestational age matched peers with normal intrauterine growth. Study design: A prospectively collected cohort of children born with FGR (birth weight &lt;10th percentile and/or abnormal umbilical artery flow, n = 28) underwent a 24-hour Holter monitoring at the mean age of 9 years and gestational age matched children with birth weight appropriate for gestational age (AGA, n = 19) served as controls. Time- and frequency domain HRV indices were measured and their associations with antenatal hemodynamic changes were analyzed. Results: Time- and frequency domain HRV parameters (standard deviation of R–R intervals, SDNN; low frequency, LF; high frequency, HF; LF/HF; very low frequency, VLF) did not differ significantly between FGR and AGA groups born between 24 and 40 weeks. Neither did they differ between children born with FGR and normal umbilical artery pulsatility or increased umbilical artery pulsatility. In total, 56% of the FGR children demonstrated blood flow redistribution (cerebroplacental ratio, CPR &lt; −2 SD) during fetal life and their SDNN (p = .01), HF (p = .03) and VLF (p = .03) values were significantly lower than in FGR children with CPR ≥ −2SD. Conclusions: Early school age children born with FGR and intrauterine blood flow redistribution demonstrated altered heart rate variability. These prenatal and postnatal findings may be helpful in targeting preventive cardiovascular measures in FGR