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 (mLmin−1kg−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 (mLmin−1kg−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.
Ultrasound biometry is an important clinical tool for the identification, monitoring, and management of fetal growth restriction and development of macrosomia. This is even truer in populations in ...which perinatal morbidity and mortality rates are high, which is a reason that much effort is put onto making the technique available everywhere, including low-income societies. Until recently, however, commonly used reference ranges were based on single populations largely from industrialized countries. Thus, the World Health Organization prioritized the establishment of fetal growth charts for international use. New fetal growth charts for common fetal measurements and estimated fetal weight were based on a longitudinal study of 1387 low-risk pregnant women from 10 countries (Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) that provided 8203 sets of ultrasound measurements. The participants were characterized by median age 28 years, 58% nulliparous, normal body mass index, with no socioeconomic or nutritional constraints (median caloric intake, 1840 calories/day), and had the ability to attend the ultrasound sessions, thus essentially representing urban populations. Median gestational age at birth was 39 weeks, and birthweight was 3300 g, both with significant differences among countries. Quantile regression was used to establish the fetal growth charts, which also made it possible to demonstrate a number of features of fetal growth that previously were not well appreciated or unknown: (1) There was an asymmetric distribution of estimated fetal weight in the population. During early second trimester, the distribution was wider among fetuses <50th percentile compared with those above. The pattern was reversed in the third trimester, with a notably wider variation >50th percentile. (2) Although fetal sex, maternal factors (height, weight, age, and parity), and country had significant influence on fetal weight (1–4.5% each), their effect was graded across the percentiles. For example, the positive effect of maternal height on fetal weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th–95th percentile for estimated fetal weight being 2205–3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts’ performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed.
To determine the prevalence of, and risk factors for anomalous insertions of the umbilical cord, and the risk for adverse outcomes of these pregnancies.
Population-based registry study.
Medical Birth ...Registry of Norway 1999-2009.
All births (gestational age >16 weeks to <45 weeks) in Norway (623,478 singletons and 11,263 pairs of twins).
Descriptive statistics and odds ratios (ORs) for risk factors and adverse outcomes based on logistic regressions adjusted for confounders.
Velamentous or marginal cord insertion. Abruption of the placenta, placenta praevia, pre-eclampsia, preterm birth, operative delivery, low Apgar score, transferral to neonatal intensive care unit (NICU), malformations, birthweight, and perinatal death.
The prevalence of abnormal cord insertion was 7.8% (1.5% velamentous, 6.3% marginal) in singleton pregnancies and 16.9% (6% velamentous, 10.9% marginal) in twins. The two conditions shared risk factors; twin gestation and pregnancies conceived with the aid of assisted reproductive technology were the most important, while bleeding in pregnancy, advanced maternal age, maternal chronic disease, female foetus and previous pregnancy with anomalous cord insertion were other risk factors. Velamentous and marginal insertion was associated with an increased risk of adverse outcomes such as placenta praevia (OR = 3.7, (95% CI = 3.1-4.6)), and placental abruption (OR = 2.6, (95% CI = 2.1-3.2)). The risk of pre-eclampsia, preterm birth and delivery by acute caesarean was doubled, as was the risk of low Apgar score, transferral to NICU, low birthweight and malformations. For velamentous insertion the risk of perinatal death at term was tripled, OR = 3.3 (95% CI = 2.5-4.3).
The prevalence of velamentous and marginal insertions of the umbilical cord was 7.8% in singletons and 16.9% in twin gestations, with marginal insertion being more common than velamentous. The conditions were associated with common risk factors and an increased risk of adverse perinatal outcomes; these risks were greater for velamentous than for marginal insertion.
Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence ...that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use.
We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range IQR 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts.
This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.
Introduction
Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous distribution, ...including increased ductus venosus shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on umbilical venous and ductus venosus flow is not known.
Material and methods
In this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36. The blood velocity and the mean diameters of the umbilical vein and ductus venosus were used for calculating blood flow volumes. The development of the umbilical venous flow, ductus venosus flow and ductus venosus shunt fraction (% of umbilical venous blood shunted through the ductus venosus) was compared with a reference population, and the effect of HbA1c on the ductus venosus flow was assessed.
Results
The umbilical venous flow was larger in pregnancies with pregestational diabetes mellitus than in low‐risk pregnancies (p < 0.001) but smaller when normalized for fetal weight (p = 0.036). The distributional pattern of the ductus venosus flow developed differently in diabetic pregnancies, particularly during the third trimester, being smaller (p = 0.007), also when normalized for fetal weight (p < 0.001). Correspondingly, the ductus venosus shunt fraction was reduced (p < 0.0001), most prominently at 36 weeks. There were negative relations between the maternal HbA1c and the ductus venosus flow velocity, flow volume and shunt fraction.
Conclusions
In pregnancies with pregestational diabetes mellitus, prioritized umbilical venous distribution to the fetal liver and lower ductus venosus shunt capacity reduce the compensatory capability of the fetus and may represent an augmented risk during hypoxic challenges during late pregnancy and birth.
To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus.
In a longitudinal ...observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24-36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160).
The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02).
The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.
Symphysis–fundus measurement: The human factor Kiserud, Torvid
BJOG : an international journal of obstetrics and gynaecology,
June 2023, 2023-06-00, 20230601, Letnik:
130, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Linked article: This is a mini commentary on Ego et al., pp. 729–739 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17399.
This longitudinal study investigated the impact of actigraphy-measured maternal physical activity on yolk sac size during early development. The yolk sac, a transient extraembryonic organ, plays a ...crucial role in embryonic development and is involved in metabolism, nutrition, growth, and hematopoiesis. Prospectively collected data from 190 healthy women indicated that their total daily physical activity, including both light and moderate-vigorous activity, was associated with yolk sac growth dynamics depending on embryonic sex and gestational age. Higher preconception maternal physical activity was linked to a larger yolk sac at 7 weeks (95% CI 0.02-0.13 mm) and a smaller yolk sac at 10 weeks' gestation (95% CI - 0.18 to - 0.00) in male embryos; in female embryos, the yolk sac size was increased at 10 weeks' gestation (95% CI 0.06-0.26) and was, on average, 24% larger than that in male embryos (95% CI 0.12-0.38). Considering the pattern of other maternal effects on yolk sac size-e.g., body composition and sleep duration-we suggest that physiological yolk sac adaptations occur in short, sex-specific time windows and can be influenced by various maternal factors.
Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes ...alters fetal liver blood flow depending on degree of glycemic control.
In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24-36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA1c assessed.
The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C.
In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.