Impacto de la diabetes mellitus en la circulación hepática fetal y nuevas opciones diagnósticas

While biometry and Doppler have proved useful in the management of fetal growth restriction, the same battery has been of less help in diabetic pregnancies. It is not surprising since the underlying pathophysiology is fundamentally different. Recent studies of the fetal liver, a key metabolic organ, have shown that its venous circulation reflects the impact of maternal hyperglycemia. Umbilical return from the placenta is disproportionately distributed to the fetal liver (more than in normally growing fetuses, and more than in non-diabetic macrosomia). However, what is set as a pattern at midtrimester is not followed up in the 3rd trimester when high fetal growth continues but no longer correspondingly supported by the umbilical flow to the liver (mL min−1 kg−1 is low). Thus, the status at 3rd trimester is as follows: umbilical flow does not match fetal growth, but the fetal liver still takes a major proportion of the placental return leaving less for the ductus venosus (DV). A distended DV does not help; rather it indicates reduced residual compensatory mechanisms to face hypoxic challenges. The new insights suggest taking into consideration the fetal liver when assessing risks in diabetic pregnancies at 3rd trimester. Measuring umbilical venous flow and its distribution requires high level of skills and accurate techniques, but in the left portal branch (between the DV inlet and the junction with the portal main stem), the blood velocity is regularly accessible and it reflects the skewed umbilical flow to the liver, and its consequences, in a graded manner.Si bien la biometría y el Doppler han demostrado ser útiles en el manejo de la restricción del crecimiento fetal, dichos exámenes han sido de menor ayuda en los embarazos en pacientes diabéticas. Esto no sorprende dado que la fisiopatología subyacente es fundamentalmente diferente. Estudios recientes del hígado fetal, un órgano metabólico clave, han demostrado que su circulación venosa refleja el impacto de la hiperglucemia materna. El retorno umbilical desde la placenta se distribuye de manera desproporcionada al hígado fetal (más que en los fetos de crecimiento normal y más que en la macrosomía no diabética). Sin embargo, lo que se establece como un patrón en el segundo trimestre no persiste en el tercer trimestre cuando al continuar el alto crecimiento no es apoyado proporcionalmente por el flujo umbilical al hígado (mL min−1 kg−1 es bajo). Por lo tanto, el estado en el tercer trimestre es el siguiente: el flujo umbilical no coincide con el crecimiento fetal, pero el hígado fetal sigue tomando una proporción importante del retorno placentario, dejando menos para el ductus venosos (DV). Un DV distendido no ayuda; más bien indica mecanismos compensatorios residuales reducidos para enfrentar desafíos hipóxicos. Los nuevos conocimientos sugieren tener en cuenta el hígado fetal al evaluar los riesgos en los embarazos diabéticos en el tercer trimestre. Medir el flujo venoso umbilical y su distribución requiere de un alto nivel de habilidad y técnicas precisas, pero en la rama portal izquierda (entre la entrada del DV y la unión con la vena porta), la velocidad de la sangre es habitualmente accesible y refleja el flujo umbilical sesgado al hígado, y sus consecuencias, de manera medible.publishedVersio

Fetal age assessment based on 2nd trimester ultrasound in Africa and the effect of ethnicity

<p>Abstract</p> <p>Background</p> <p>The African population is composed of a variety of ethnic groups, which differ considerably from each other. Some studies suggest that ethnic variation may influence dating. The aim of the present study was to establish reference values for fetal age assessment in Cameroon using two different ethnic groups (Fulani and Kirdi).</p> <p>Methods</p> <p>This was a prospective cross sectional study of 200 healthy pregnant women from Cameroon. The participants had regular menstrual periods and singleton uncomplicated pregnancies, and were recruited after informed consent. The head circumference (HC), outer-outer biparietal diameter (BPDoo), outer-inner biparietal diameter and femur length (FL), also called femur diaphysis length, were measured using ultrasound at 12–22 weeks of gestation. Differences in demographic factors and fetal biometry between ethnic groups were assessed by t- and Chi-square tests.</p> <p>Results</p> <p>Compared with Fulani women (N = 96), the Kirdi (N = 104) were 2 years older (p = 0.005), 3 cm taller (p = 0.001), 6 kg heavier (p < 0.0001), had a higher body mass index (BMI) (p = 0.001), but were not different with regard to parity. Ethnicity had no effect on BPDoo (p = 0.82), HC (p = 0.89) or FL (p = 00.24). Weight, height, maternal age and BMI had no effect on HC, BPDoo and FL (p = 0.2–0.58, 0.1–0.83, and 0.17–0.6, respectively).</p> <p>When comparing with relevant European charts based on similar design and statistics, we found overlapping 95% CI for BPD (Norway & UK) and a 0–4 day difference for FL and HC.</p> <p>Conclusion</p> <p>Significant ethnic differences between mothers were not reflected in fetal biometry at second trimester. The results support the recommendation that ultrasound in practical health care can be used to assess gestational age in various populations with little risk of error due to ethnic variation.</p

Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction

Background: Fetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. Aim: Echocardiographic assessment of heart function in FGR neonates first three days after birth. Study design: Prospective observational study. Subjects: FGR- and non-FGR neonates. Outcome measures: M-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e′ of the atrioventricular plane day one, two and three after birth. Results: Compared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e′ (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e′ (15 (7) %, p = 0.049), right a′ (18 (6) %, p = 0.001), left E/e′ (25 (10) %, p = 0.015) and right E/e′ (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. Conclusions: FGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.publishedVersio

Sex-specific reference ranges of cerebroplacental and umbilicocerebral ratios: A longitudinal study

This is the peer reviewed version of the following article: Acharya, G., Ebbing, C., Karlsen, H., Kiserud, T. & Rasmussen, S. (2019). Sex-specific reference ranges of cerebroplacental and umbilicocerebral ratios: A longitudinal study. Ultrasound in Obstetrics and Gynecology, 2019, which has been published in final form at https://doi.org/10.1002/uog.21870. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Objectives - The ratio of middle cerebral artery (MCA) pulsatility index (PI) to umbilical artery (UA) PI, i.e. cerebro‐placental ratio (CPR), has been suggested as a measure of fetal “brain sparing” phenomenon reflecting redistribution of fetal cardiac output as a response to placental insufficiency. Observational studies have shown that low CPR values predict increased risk of adverse perinatal outcomes although evidence from randomized clinical trials is lacking. The inverse ratio, i.e. umbilico‐cerebral ratio (UCR), is preferred by some as it increases with increasing degree of fetal compromise. Monitoring fetal wellbeing requires serial assessment, and for this purpose, appropriate reference values should be based on data from longitudinal studies. However, longitudinal reference ranges for the UCR have not been established. Furthermore, the sex of the fetus influences its growth velocity, cord properties, in utero circadian rhythm, behavioral states and placental function, but whether gestational age‐dependent changes in CPR or UCR differ between male and female fetuses has not been studied. Thus, our objective was to investigate sex‐specific, gestational age‐associated serial changes in CPR and UCR during the second half of pregnancy and establish longitudinal reference ranges. Methods - This was a dual‐center prospective longitudinal study of singleton low risk pregnancies. Doppler blood flow velocity waveforms were obtained serially from the UA and MCA during 19‐41 weeks of gestation, and PIs were determined. CPR and UCR were calculated as the ratios, MCA PI/ UA PI and UA PI/ MCA PI, respectively. The course and outcome of pregnancies was recorded. Sex of the fetus was determined after delivery. Reference intervals were constructed using multilevel modelling and gestational age‐specific Z‐scores of male and female fetuses were compared. Results - Of a total of 299 pregnancies enrolled, 284 women and their fetuses (148 male and 136 female) were included in the final analysis, and 979 paired measurements of UA and MCA PIs were used to construct sex‐specific longitudinal reference intervals. Both CPR and UCR had U‐shaped curves of development during pregnancy, but with opposite directions. There was a small but significant (P=0.007) difference in z‐scores of CPR and UCR between male and female fetuses throughout the second half of pregnancy. Conclusions - We have established longitudinal reference ranges for CPR and UCR suitable for serial monitoring with possibilities to refine the assessment by fetal sex‐specific ranges and the conditioning by a previous measurement. The clinical significance of such refinements needs further evaluation

Fetal Superior Vena Cava Blood Flow and Its Fraction of Cardiac Output: A Longitudinal Ultrasound Study in the Second Half of Pregnancy

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (QSVC) comes from the brain. To provide the possibility of using this blood flow as a representation of fetal brain circulation, we aimed to determine the fetal QSVC and its fraction of cardiac output during the second half of physiological pregnancies. Materials and Methods: This was a prospective longitudinal study specifically designed for studying fetal hemodynamic development. Healthy women with singleton low-risk pregnancies were included. Ultrasonography was performed at 4-weekly intervals from 20+0 gestational weeks to term. Doppler velocity recordings of the superior vena cava (SVC) and cardiac ventricular outflow tracts were used to obtain the time-averaged maximum velocities (TAMxV). Vessel diameters were measured to calculate their cross-sectional areas (CSA): π(diameter/2)2. Blood flow (Q) was computed as: h*TAMxV*CSA, h being the spatial blood velocity profile, to obtain QSVC and cardiac outputs. The sum of left and right ventricular cardiac outputs constituted the combined cardiac output (CCO). Ultrasound biometry based estimated fetal weight and brain weight were used to normalize the flow. QSVC was also expressed as the fraction (%) of CCO. Gestational age specific percentiles were established for each blood flow parameter using multilevel modeling. Results: Totally, 134 of the 142 included women were eligible for the study with 575 sets of observations. The SVC mean diameter (19–52 mm), mean TAMxV (8.83–16.14 cm/s), and QSVC (15.4–192.0 ml/min) increased significantly during the second half of pregnancy (p < 0.001) while the mean QSVC normalized by estimated fetal weight (49 ml/min/kg) and by estimated brain weight (50 ml/min/100 g) were relatively stable. Similarly, the mean CCO increased (156–1,776 ml/min; p < 0.001) while the normalized CCO (509 ± 13 ml/min/kg) and QSVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age. Conclusion: We provide reference values for fetal QSVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy.publishedVersio

Optimal fetal growth – a misconception?

Alterations in fetal growth trajectory, either in terms of individual organs or the fetal body, constitute part of a suite of adaptive responses that the fetus can make to a developmental challenge such as inadequate nutrition. Nonetheless, despite substantial changes in nutrition in many countries over recent centuries, mean birthweight has changed relatively little. Low birthweight is recognised as a risk factor for later noncommunicable disease, although the developmental origins of such risk are graded across the full range of fetal growth and birthweight. Many parental and environmental factors, some biological, some cultural, can influence fetal growth, and these should not be viewed as abnormal. We argue that the suggestion of establishing a universal standard for optimal fetal growth ignores the breadth of these normal fetal responses. It may influence practice adversely, through incorrect estimation of gestational age and unnecessary elective deliveries. It raises ethical as well as practical issues

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study

Background - Fetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy. Methods - This was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20–41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated. Results - SVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy. Conclusions - Longitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term

Sleep and physical activity from before conception to the end of pregnancy in healthy women: a longitudinal actigraphy study

Background Sleep and physical activity changes are common in pregnancy, but longitudinal data starting before conception are scarce. Our aim was to determine the changes of the daily total sleep time (TST) and physical activity duration (PAD) from before conception to end of pregnancies in respect of pregestational maternal factors. Methods This longitudinal observational study formed part of the CONIMPREG research project and recruited healthy women planning to become pregnant. Sleep and physical activity were recorded around-the-clock for ≥4 days via actigraphy before conception and during each trimester of pregnancy. Data were adjusted according to pregestational maternal body composition, parity and age. Results Among 123 women with eligible data, the unadjusted mean (95% confidence interval) TST increased from 415.3 min (405.5–425.2 min) before conception to 458.0 min (445.4–470.6 min) in the 1st trimester, remaining high through the 2nd and 3rd trimesters. Variation was substantial before conception (±2SD range: 307–523 min). The unadjusted mean PAD before conception was 363.7 min (±2SD range: 120–608 min), decreasing sharply to 262.1 min in the first trimester and more gradually thereafter. Vigorous and moderate activity decreased more than light activity. TST and PAD were significantly associated with age, parity, and pregestational body fat percentage; lean body mass was negatively correlated with TST. Results were generally unaffected by seasonal variations. Conclusion Marked variations were found in pregestational TST and PAD. Healthy women slept ≥30 min longer during pregnancy, while PAD decreased by ≥ 90 min in early pregnancy and continued to decrease thereafter.publishedVersio

Cardiac morphology in neonates with fetal growth restriction

Objective: Assess effects of fetal growth restriction (FGR) on cardiac modelling in premature and term neonates. Study design: Prospective echocardiographic study of a cohort of FGR neonates (n = 21) and controls (n = 41) with normal prenatal growth and circulation. Results: Unadjusted for gestational age, birth weight, sex, and twin/singleton, Late-FGR neonates had smaller hearts than controls, with globular left ventricles and symmetrical right ventricles. Adjusted estimates showed smaller left ventricles and similarly sized right ventricles, with symmetrical left and right ventricles. Early-FGR (compared with Late-FGR) had smaller hearts and globular left ventricles in unadjusted estimates, but after adjustment, sizes and shapes were similar. Conclusion: FGR had significant impact on cardiac modelling, seen in both statistical models unadjusted and adjusted for gestational age, birth weight, sex, and twin/singleton. The adjustments, however, refined the results and revealed more specific effects of FGR, thus underscoring the importance of statistical adjustments in such studies.acceptedVersio