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Objective: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC).

Design: Longitudinal population-based cohort study.

Setting: Swedish national registers.

Population: A total of 196 008 singleton pregnancies between 2013 and 2017.

Methods: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders.

Main Outcome: MeasuresFetal growth velocity. SGA, LGA and macrosomia.

Results: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET.

Conclusions: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed.

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.

Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire.

Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.

This study investigated whether maternal central adiposity and body mass index (BMI) were associated with neonatal hypoglycemia and adverse neonatal outcomes. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015 and 2018. Visceral and subcutaneous fat depths were measured by ultrasound at the early second-trimester anomaly scan in 2771 women giving birth to singleton infants. Body mass index was assessed in early pregnancy. Logistic regression models were performed. Adjustments were made for age, BMI (not in model with BMI as exposure), smoking, maternal country of birth, and parity. Outcomes were neonatal hypoglycemia (blood glucose concentration < 2.6 mmol/l), a composite of adverse neonatal outcomes (Apgar < 7 at 5 min of age, or umbilical artery pH ≤ 7.0, or admission to neonatal intensive care unit), and the components of the composite outcome. Visceral and subcutaneous fat depths measured by ultrasound in early mid pregnancy were not associated with any of the outcomes in adjusted analyses. For every unit increase in BMI, the likelihood of neonatal hypoglycemia increased by 5% (aOR 1.05, 95% CI 1.01–1.10), the composite outcome by 5% (aOR 1.05, 95% CI 1.01–1.08), and admission to neonatal intensive care unit by 6% (aOR 1.06, 95% CI 1.02–1.10).

Introduction Two-thirds of induced abortions after gestational week (gw) 18 are performed due to fetal anomalies. The potential of the fetus to survive outside the uterus after birth is the upper limit for induced abortions in Sweden. Due to advances in neonatal medicine, fetal viability and the upper limit of late induced abortions have been converging over the last few decades. The aim of the study was to examine clinical management of fetal anomalies, including time frames, leading to second trimester abortions.

Material and methods All induced abortions due to fetal anomalies after gw 11+6 in Uppsala county, Sweden, from 2010 to 2017, were reviewed from electronic medical records in a retrospective descriptive study. In total, 180 women underwent 185 abortions divided into 107 (57.8%) in an early group (gw 12+0 to 18+0), and 78 (42.2%) in a late group (≥ gw 18+1). Examinations performed were genetic testing, fetal echocardiography, magnetic resonance imaging (MRI) and pediatric counseling. Time frames from suspicion of fetal anomaly to abortion were reviewed.

Results Anomalies were subdivided into groups of diagnosis: chromosomal (n = 104), central nervous system (n = 22), heart (n = 12), urinary tract (n = 10) and others (n = 37). Chromosomal anomaly was present in 82 (76.6%) in the early group and 22 (28.2%) in the late group. In the early group, examinations performed preceding a conclusive diagnosis were mainly QF-PCR for trisomies (n = 97), microarray (n = 13), and genetic counseling (n = 14). In the late group, trisomy test was performed in 68, microarray in 31, MRI in 24, fetal echocardiography in 28, and pediatric or genetic counseling in 43 and six cases, respectively.

Mean time interval from suspicion of fetal anomaly to the woman’s decision was 5 days before gw 18+1, 7 days in gw 18, and 13 days in gw 21. More than two examinations before reaching the decision to terminate the pregnancy were needed in two abortions (25.0%) in gw 18, increasing to 16 (80.0%) in gw 21.

Conclusions Increasing complexity and diversity in fetal diagnoses require time-consuming examinations in late-induced abortions compared with earlier gestational weeks. A structured expedient process is necessary to allow for decision time and minimize terminations approaching the legal limit.

Fetal growth restriction is a strong risk factor for perinatal morbidity and mortality. Reliable standards are indispensable, both to assess fetal growth and to evaluate birthweight and early postnatal growth in infants born preterm. The aim of this study was to create updated Swedish reference ranges for estimated fetal weight (EFW) from gestational week 12-42. This prospective longitudinal multicentre study included 583 women without known conditions causing aberrant fetal growth. Each woman was assigned a randomly selected protocol of five ultrasound scans from gestational week 12 + 3 to 41 + 6. Hadlock's 3rd formula was used to estimate fetal weight. A two-level hierarchical regression model was employed to calculate the expected median and variance, expressed in standard deviations and percentiles, for EFW. EFW was higher for males than females. The reference ranges were compared with the presently used Swedish, and international reference ranges. Our reference ranges had higher EFW than the presently used Swedish reference ranges from gestational week 33, and higher median, 2.5th and 97.5th percentiles from gestational week 24 compared with INTERGROWTH-21st. The new reference ranges can be used both for assessment of intrauterine fetal weight and growth, and early postnatal growth in children born preterm.

We sought to investigate whether early mid pregnancy visceral and subcutaneous fat depths measured by ultrasound were associated with infant birth size, independent of early pregnancy BMI. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015-2018. Visceral and subcutaneous fat depths were measured at the early second-trimester anomaly scan in 2498 women, giving birth to singleton, term infants. Primary outcomes were birthweight and LGA (birthweight standard deviation score>90th percentile in the cohort). Linear and logistic regression models were used, adjusted for BMI, age, smoking, parity, maternal country of birth, gestational age and infant sex. A 5-mm increase in visceral fat depth was associated with an increase in birthweight of 8.3 g [95% confidence interval (CI) 2.5-14.1 g], after adjustments, and a 6% increase in the adjusted odds of having an infant born LGA (OR 1.06, CI 1.02-1.11). There was no association between subcutaneous fat depth and birthweight or LGA after covariate adjustments. Hence, visceral fat depth measured by ultrasound in early mid pregnancy was associated with excessive fetal growth, independent of early pregnancy BMI, and may be useful in models for predicting LGA infants.

Objectives To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. Methods This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32+ 0 to 36+ 6weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. Results The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n= 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33weeks and 1.0 at 34-36weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. Conclusion In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. (C) 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasonic assessment of fetal growth is an important part of obstetric care to prevent adverse pregnancy outcome. However, lack of reliable reference ranges is a major barrier for accurate interpretation of the examinations. The aim of this study was to create updated Swedish national reference ranges for intrauterine size and growth of the fetal head, abdomen and femur from gestational week 12 to 42.

This prospective longitudinal multicentre study included 583 healthy pregnant women with low risk of aberrant fetal growth. Each woman was examined up to five times with ultrasound from gestational week 12+3 to 41+6. The assessed intrauterine fetal biometric measurements were biparietal diameter (outer-inner), head circumference, mean abdominal diameter, abdominal circumference and femur length. A two-level hierarchical regression model was employed to account for the individual measurements of the fetus and the number of repeated visits for measurements while accounting for the random effect of the identified parameterization of gestational age. The expected median and variance, expressed in both standard deviations and percentiles, for each individual biometric measurement was calculated. 

The presented national reference ranges can be used for assessment of intrauterine size and growth of the fetal head, abdomen and femur in the second and third trimester of pregnancy.

Today we lack knowledge if size at birth and gestational age interacts regarding postnatal growth pattern in children born at 32 gestational weeks or later.

This population-based cohort study comprised 41,669 children born in gestational weeks 32-40 in Uppsala County, Sweden, between 2000 and 2015. We applied a generalized least squares model including anthropometric measurements at 1.5, 3, 4 and 5 years. We calculated estimated mean height, weight and BMI for children born in week 32+0, 35+0 or 40+0 with birthweight 50^th percentile (standardized appropriate for gestational age, sAGA) or 3^rd percentile (standardized small for gestational age, sSGA).

Compared with children born sAGA at gestational week 40+0, those born sAGA week 32+0 or 35+0 had comparable estimated mean height, weight and BMI after 3 years of age. Making the same comparison, those born sSGA week 32+0 or 35+0 were shorter and lighter with lower estimated mean BMI throughout the whole follow-up period.

Our findings suggest that being born SGA and moderate preterm is associated with short stature and low BMI during the first five years of life. The association seemed stronger the shorter gestational age at birth.

Background: Maternal smoking impairs fetal growth; however, if postnatal growth differs between children born small for gestational age (SGA) with smoking and non-smoking mother is unknown.

Methods: Cohort-study of term born children born appropriate for gestational age with non-smoking mother (AGA-NS, n=30,561), SGA (birthweight <10^th percentile) with smoking mother (SGA-S, n=171) or SGA with non-smoking mother (SGA-NS, n=1761). Means of height and weight measurements, collected at birth, 1.5, 3, 4 and 5 years, were compared using a generalized linear mixed effect model. Relative risks of short stature (<10^th percentile) were expressed as adjusted risk ratios (aRR).

Results: At birth, children born SGA-S were shorter than SGA-NS, but they did not differ in weight. At 1.5 years, SGA-S had reached the same height as SGA-NS. At 5 years, SGA-S were 1.1 cm taller and 1.2 kg heavier than SGA-NS. Compared with AGA-NS, SGA-S did not have increased risk of short stature at 1.5 or 5 years, while SGA-NS had increased risk of short stature at both ages; aRRs 3.0 (95% CI 2.6;3.4) and 2.3 (95% CI 2.0;2.7), respectively.

Conclusions: Children born SGA-S have a more rapid catch-up growth than SGA-NS. This may have consequences for metabolic and cardiovascular health in children with smoking mothers.