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This article, published in the journal Ultrasound in Obstetrics & Gynecology, discusses a study conducted at Stavanger University Hospital from June 2020 to May 2023. The study aimed to establish longitudinal reference ranges for the pulsatility index (PI) of the fetal inferior adrenal artery using a new ultrasound technique. The researchers enrolled 150 participants with low-risk singleton pregnancies and conducted sonographic examinations every 4-6 weeks from 19 weeks gestation until delivery. The study found that the longitudinal reference ranges for the fetal inferior adrenal artery PI could potentially be used as a tool for improved monitoring of fetal growth restriction. [Extracted from the article]

An abstract of the article "Thermal index for bone for diagnostic scanners: actual ranges of ultrasound intensity measured in vitro" by K. Retz is presented.

Aim Fetoplacental Doppler abnormalities have been associated with increased neonatal mortality and morbidity. This study evaluated the associations between prenatal Doppler assessments and neonatal mortality and morbidity in premature infants born small for gestational age or after pre-eclampsia. Methods This was a population-based study of infants born alive at 220-336 weeks of gestation, a birthweight <10th percentile for gestational age and/or maternal pre-eclampsia. Doppler assessments of the umbilical artery, middle cerebral artery and ductus venosus were evaluated in 127, 125 and 95 cases, respectively. Circulatory compromise was defined as absent or reversed end-diastolic velocity in the umbilical artery ( AREDF), middle cerebral artery pulsatility index <2.5 percentile for gestational age and ductus venosus pulsatility index for veins >97.5 percentile. Results AREDF was present in 28% of the infants. This was associated with increased frequencies of neonatal sepsis and necrotising enterocolitis after adjusting for gestational age. Abnormal ductus venosus pulsatility index for veins was associated with increased risk of neonatal sepsis, but only in combination with AREDF. These associations were only present when gestational age was <28 weeks. Conclusion AREDF was associated with increased neonatal morbidity in premature infants born small for gestational age or after pre-eclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Detection and surveillance of fetal growth restriction (FGR) is well established, but there is still room for improvement. Animal studies indicate that compromised fetuses increase adrenal blood flow. Modern ultrasound equipment allows us to measure vascular impedance in the fetal adrenal arteries despite their modest size. However, extensive anatomical variance is a challenge to standardizing measurements. We set out to improve this., Material and Methods: We included 75 low-risk pregnant women in a prospective cross-sectional study aiming to develop a reliable technique to visualize and measure flow velocity in human fetal adrenal arteries. We used commercially available ultrasound equipment: a GE Voluson 10 2019 with a C2-9 probe (GE Healthcare, Zipf, Austria), and a Philips Epiq Elite with a V9-2 probe (Philips Medical Systems International B.V., Best, The Netherlands), exploiting the modern sensitive power Doppler modes in both scanners to visualize small vessels., Results: Among 72 fetuses, the inferior adrenal artery was the most consistently visualized and measured artery to the gland. Doppler velocimetry was achieved in 66 (92%) participants. We found the anatomical variation described previously but were able to develop visualization strategies to identify the common arteries and use a consistent Doppler technique for the second half of pregnancy., Conclusions: It is possible to visualize and measure flow velocity in the adrenal arteries of human fetuses. The success rate was highest for the inferior adrenal artery making this vessel a candidate for clinical studies., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The concept of developmental origin of health and disease has ignited a search for mechanisms and health factors influencing normal intrauterine development. Sleep is a basic health factor with substantial individual variation, but its implication for early prenatal development remains unclear. During the embryonic period, the yolk sac is involved in embryonic nutrition, growth, hematopoiesis, and likely in fetal programming. Maternal body measures seem to influence its size in human female embryos. In this prospective, longitudinal observational study of 190 healthy women recruited before natural conception, we assessed the effect of prepregnant sleep duration (actigraphy) on the fetal crown-rump-length (CRL) and yolk sac size (ultrasound). All women gave birth to a live child. The prepregnancy daily sleep duration had an effect on the male yolk sac and CRL at the earliest measurement only (7 weeks). I.e., the yolk sac diameter decreased with increasing sleep duration (0.22 mm·h -1 d -1 , 95%CI [0.35-0.09], P < 0.01), and CRL increased (0.92 mm·h -1 d -1 , 95%CI [1.77-0.08], P = 0.03). Since there was no association at the second measurement (10 weeks), and in the group of female fetuses at any measure point, we suggest a sex- and time-dependent embryonic adaptation to sleep generated differences in the intrauterine environment in normal pregnancies., (© 2022. The Author(s).)

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: 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., Methods: 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)., Results: 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)., Conclusions: 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., Competing Interests: The authors have declared that no competing interests exist.

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (Q SVC ) 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 Q SVC 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 Q SVC 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. Q SVC 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 Q SVC (15.4-192.0 ml/min) increased significantly during the second half of pregnancy ( p < 0.001) while the mean Q SVC 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 Q SVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age. Conclusion: We provide reference values for fetal Q SVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stefopoulou, Johnson, Herling, Lindgren, Kiserud and Acharya.)

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 1 st trimester, remaining high through the 2 nd and 3 rd 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., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

Introduction: Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR., Material and Methods: In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41 weeks. The CPR was calculated as PI MCA /PI UA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as Q SVC /Q UV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling., Results: Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of Q SVC and Q UV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R = 0.10; P = .051), or UCR and Q-UCR (R = 0.09; P = .11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor., Conclusions: Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further., (© 2020 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Gynaecological fistulae cause urinary and/or faecal incontinence. Haukeland University Hospital has systematically recorded treatments for gynaecological fistulae, since 2012 in its capacity as the Norwegian National Unit for Gynaecological Fistulae. This study describes characteristics of and therapeutic outcomes for gynaecological fistulae caused by surgery and/or radiotherapy., Material and Method: We have conducted a retrospective cohort study of women who were treated at the Department of Gynaecology and Obstetrics, Haukeland University Hospital, in the period 1995-2019 for gynaecological fistulae due to surgery or radiotherapy., Results: Surgery or radiotherapy was the cause of gynaecological fistulae in 182 of a total of 411 women. 163 of them consented to the study, 124/163 (76 %) with fistulae following surgery and 39/163 (24 %) with fistulae following radiotherapy. The post-surgical fistulae were mainly urogenital (91/124: 73 %) and most often caused by a hysterectomy (n = 71) or urinary incontinence procedure (n = 11). Post-radiotherapy fistulae were mainly enterogenital (34/39: 87 %), with rectal cancer (n = 22) and cervical cancer (n = 11) as the most frequent types of cancer. The main procedure was vaginal fistuloplasty, which was carried out on 100/124 (81 %) of women with post-surgical fistula and 7/39 (18 %) of those with post-radiotherapy fistula. Catheter drainage or stomy alone resulted in healing in 14/163 (9 %) of all patients. A total of 117/124 (94 %) of women with post-surgical fistula achieved healing, compared with 10/39 (26 %) with post-radiotherapy fistula. 28/39 (72 %) of the latter had a permanent urostomy or enterostomy., Interpetation: Gynaecological fistulae caused by surgery have a good healing rate, while post-radiotherapy fistulae are more often permanent.

Introduction: Gynecological fistula (affecting female genital organs) leads to involuntary loss of urine or feces. In industrialized societies, fistulas occur mostly as complications of surgery, radiation therapy or inflammatory bowel disease. We sought to determine the incidence of gynecological fistula and type of surgical treatment provided in Norway., Material and Methods: This was a retrospective national cohort study of women treated for gynecological fistula (International Classification of Disease-10 code N82) during 2008-2014, identified from the mandatory Norwegian Patient Registry. To compare groups, we utilized Chi-square or non-parametric tests., Results: In all, 1627 women (.06% of the female Norwegian population) had 4475 hospital admissions with a diagnosis of gynecological fistula. In total, 1214/1627 (75%) had fistula as the main diagnosis: 346 (29%) a urogenital fistula, 672 (55%) an enterogenital, 38 (3%) a genitocutaneous and 22 (2%) both urinary and enteral fistula. Surgery for gynecological fistula was performed in 723 women, an incidence rate of 4.2 per 100 000 person-years (95% confidence interval [CI] 4.2-4.3); gynecological procedures (mostly vaginal/perineal) were performed in 163 women (23%), urological in 43 (6%), enteral in 267 (37%) and surgery involving multiple pelvic compartments in 250 (35%). Women undergoing fistula surgery had a median of three hospital contacts (95% CI 3-3), for 370 women (52%), the procedure was performed by a gynecologist, and 212 of these (29%) were also operated by urologists or gastroenterologists., Conclusions: Gynecological fistula is rare in Norway, with an overall incidence of 6/10 000 in the female population, whereas the incidence of surgically treated fistula is 4.2/100 000. However, the condition represents considerable morbidity for the individual patient., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Circadian rhythmicity is fundamental to human physiology, and is present even during fetal life in normal pregnancies. The impact of maternal endocrine disease on the fetal circadian rhythm is not well understood. The present study aimed to determine the fetal circadian rhythm in pregnancies complicated by pregestational diabetes mellitus (PGDM), compare it with a low-risk reference population, and identify the effects of maternal glycemic control and morning cortisol concentrations. Long-term fetal electrocardiogram recordings were made in 40 women with PGDM at 28 and 36 weeks of gestation. Two recordings were made in 18 of the women (45.0%) and one recording was made in 22 (55.0%). The mean fetal heart rate (fHR) and the fHR variation (root mean square of squared differences) were extracted in 1-min epochs, and circadian rhythmicity was detected by cosinor analysis. The study cohort was divided based on HbA1c levels and morning cortisol concentrations. Statistically, significant circadian rhythms in the fHR and the fHR variation were found in 45 (100%) and 44 (95.7%) of the 45 acceptable PGDM recordings, respectively. The rhythms were similar to those of the reference population. However, there was no statistically significant population-mean rhythm in the fHR among PGDM pregnancies at 36 weeks, indicating an increased interindividual variation. The group with higher HbA1c levels (>6.0%) had no significant population-mean fHR rhythm at 28 or 36 weeks, and no significant fHR-variation rhythm at 36 weeks. Similarly, the group with a lower morning cortisol concentration (≤8.8 µg/dl) had no significant population-mean fHR-variation rhythm at 28 and 36 weeks. These findings indicate that individual fetal rhythmicity is present in pregnancies complicated by PGDM. However, suboptimal maternal glycemic control and a lower maternal morning cortisol concentration are associated with a less-well-synchronized circadian system of the fetus.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The human yolk sac provides the embryo with stem cells, nutrients, and gas exchange. We hypothesized that more maternal resources, reflected in body size and body composition, would condition a a larger yolk sac, ensuring resources for the growing embryo. Thus, we aimed to determine the relation between maternal size in early pregnancy and yolk sac size., Material and Methods: This subsidiary study was embedded in the multinational World Health Organization fetal growth project that included healthy women with a body mass index of 18-30, reliable information of their regular last menstrual period and singleton pregnancies. Yolk sac diameter, crown-rump length, and maternal height, weight, body mass index, and body composition were assessed before 13 weeks of gestation, and the fetal biometry was repeated during the pregnancy., Results: Of 140 participants, 122 with a successful yolk sac measurement were entered in the present analysis. Maternal weight was negatively associated with the yolk sac diameter (P = 0.007) and so was maternal height (P = 0.011), fat mass (P = 0.037), and lean body mass (P = 0.018), but not body mass index (P = 0.121). Significant effects were predominantly due to the female embryos and could be traced at 24 weeks of gestation. That is, a small yolk sac : crown-rump length ratio in early pregnancy was associated with a high fetal abdominal circumference (P < 0.001) and estimated fetal weight (P = 0.001)., Conclusions: The human yolk sac is involved in the regulation of embryonic growth, but contrary to our hypothesis, the yolk sac has a compensatory capacity, being larger when the mothers are smaller; and the effect can be traced on fetal size at 24 weeks of gestation., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Fetal biometry is used for determining gestational age and estimated date of delivery (EDD). However, the accuracy of the EDD depends on the assumed length of pregnancy included in the calculation. This study aimed at assessing the actual pregnancy length and accuracy of EDD prediction based on fetal head circumference measured at the second trimester., Material and Methods: This was a population-based observational study with the following inclusion criteria: singleton pregnancy, head circumference dating in the second trimester, spontaneous onset or induction of delivery ≥ 294 days of gestation, live birth. The EDD was set anticipating a pregnancy length of 282 days. Bias in the prediction of EDD was defined as the difference between the actual date of birth and the EDD., Results: Head circumference measurements were available for 21 451 pregnancies. Ultrasound-dated pregnancies had a median pregnancy length of 283.03 days, corresponding to a method bias of 1.03 days (95% CI; 0.89-1.16). This bias was dependent on the head circumference at dating, ranging from -1.58 days (95% CI; -3.54 to 1.12) to 3.42 days (95% CI; 1.98-4.31). The median pregnancy length, based on the last menstrual period of women with a regular menstrual cycle (n = 12 985), was 283.15 days (95% CI; 282.91-283.31). A total of 5685 (22.9%, 95% CI; 22.4% to 23.4%) and 886 women (3.6%, 95% CI; 3.3%-3.8%) were still pregnant 7 and 14 days after the EDD, respectively., Conclusions: Second trimester head circumference measurements can be safely used to predict EDD. A revision of the pregnancy length to 283 days will reduce the bias of EDD prediction to a level comparable with other methods., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

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 HbA 1c 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 HbA 1c 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., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Sexual dimorphism in placental size and function has been described. Whether this influences the clinically important umbilical artery (UA) waveform remains controversial, although a few cross-sectional studies have shown sex differences in UA pulsatility index (PI). Therefore, we tested whether fetal sex influences the UA Doppler indices during the entire second half of pregnancy and aimed to establish sex-specific reference ranges for UA Doppler indices if needed., Methods: Our main objective was to investigate gestational age-associated changes in UA Doppler indices during the second half of pregnancy and compare the values between male and female fetuses. This was a prospective longitudinal study in women with singleton low-risk pregnancies during 19-40 weeks of gestation. UA Doppler indices were serially obtained at a 4-weekly interval from a free loop of the umbilical cord using color-directed pulsed-wave Doppler ultrasonography. Sex-specific reference intervals were calculated for the fetal heart rate (HR), UA PI, resistance index (RI), and systolic/diastolic ratio (S/D) using multilevel modeling., Results: Complete data from 294 pregnancies (a total of 1261 observations from 152 male and 142 female fetuses) were available for statistical analysis, and sex-specific reference ranges for the UA Doppler indices and fetal HR were established for the last half of pregnancy. UA Doppler indices were significantly associated with gestational age (P < 0.0001) and fetal HR (P < 0.0001). Female fetuses had 2-8% higher values for UA Doppler indices than male fetuses during gestational weeks 20 +0 -36 +6 (P < 0.05), but not later. Female fetuses had higher HR from gestational week 26 +0 until term (P < 0.05)., Conclusions: We have determined gestational age-dependent sex differences in UA Doppler indices and fetal HR during the second half of pregnancy, and correspondingly established new sex-specific reference ranges intended for refining diagnostics and monitoring individual pregnancies.

Introduction: The question of whether universal growth charts can be used in multi-ethnic settings is of general interest. The Intergrowth-21st fetal growth and newborn size standards are suggested to represent optimal fetal growth regardless of country origin. Our aim was to examine whether women fulfilling the strict Intergrowth-21st inclusion criteria were healthier, showed less ethnic differences in fetal growth and newborn size, and less adverse perinatal outcomes., Material and Methods: Data were drawn from a population-based multi-ethnic cohort of 823 presumably healthy pregnant women in Oslo, Norway. We assessed differences in fetal and neonatal gestational age specific z-scores and compared maternal health parameters, pregnancy and birth complications between pregnancies fulfilling and not fulfilling the Intergrowth-21st criteria., Results: Only 21% of pregnancies enrolled in our cohort fulfilled the Intergrowth-21st criteria. Fetal growth deviated substantially from the new standards, in particular for ethnic Europeans. Ethnic differences persisted in pregnancies fulfilling the criteria. In South Asian fetuses, estimated fetal weight was -0.60 SD (95% confidence interval -1.00, -0.20) lower at 24 gestational weeks, and birthweight was -0.62 SD (-0.95, -0.29) lower, compared with ethnic Europeans. Corresponding numbers for Middle-East/North Africans were -0.13 (-0.62, 0.36) and -0.60 (-1.00, -0.20). Maternal health indicators and birth complications were similar in women fulfilling and not fulfilling the criteria, but the relation depended on ethnic origin., Conclusions: In an urban multi-ethnic Norwegian population, applying an extensive list of criteria to define "healthy" pregnancies excludes the majority of women but does not cancel ethnic differences in fetal growth., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

Background: 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., Methods and Findings: 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., Conclusions: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: GP is a WHO statistical consultant and has a contract to give statistical support to the Fetal Growth Study. GP has worked with WHO for 15 years and has a relationship with WHO, both paid (contracts) and unpaid. GP is also a good friend of many of the investigators involved in this study. LDP is a Board Member of the Perinatal Quality Foundation, a nonprofit organization related to the Society for Maternal Fetal Medicine. LDP has received research support from General Electric Medical Systems unrelated to fetal growth. LDP also lectures 1 or 2 times per year at an educational meeting supported by General Electric Medical Systems unrelated to fetal growth.

Introduction: The new Holter monitoring technology enables long-term electrocardiographic recording of the fetal heart rate without discomfort for the mother. The aim of the study was to assess the feasibility of a fetal Holter monitor. This technology was further used to study fetal heart rate outside the hospital setting during normal daily activities and to test the hypothesis that uterine activity during pregnancy influences fetal heart rate., Material and Methods: Prospective observational study including 12 healthy pregnant women at 20-40 weeks of gestation. Data were collected using the Monica AN24 system. Outcome measures were fetal heart rate, maternal heart rate, and uterine activity categorized according to the strength of the electrohysterographic signal., Results: The recordings had a median length of 18.8 h, and fetal heart rate and maternal heart rate were obtained with success rates of 73.1 and 99.9%, respectively. Uterine activity was found to affect fetal heart rate in all participants. Compared with the basal tone and mild levels of uterine activity, moderate and strong levels of uterine activity were associated with increases in fetal heart rate of 4.0 and 5.7 beats/min, respectively. At night, the corresponding increases were 4.9 and 7.6 beats/min. Linear correlations were found between maternal heart rate and fetal heart rate in 11 of the 12 cases, with a mean coefficient beta of 0.189. Both maternal heart rate and fetal heart rate exhibited a diurnal pattern, with lower heart rates being recorded at night., Conclusions: Uterine activity during pregnancy is associated with a graded response in fetal heart rate and may represent a physiological challenge for the development and adaptation of the fetal cardiovascular system., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)