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Abnormal fetal growth is closely related to adverse short-term outcomes as well as negative long-term health consequences. Fetal growth restriction is a common pregnancy complication, and for the detection of fetuses small for gestational age, a reliable reference is vital. Increasing evidence supports that mode of conception has implications for growth. Fresh embryo transfer (ET) is associated with small for gestational age, and frozen ET with large for gestational age. The overall aim of this thesis was to describe optimal fetal growth, as well as pre-and postnatal growth after ART, trying to isolate the direct effects of ART from related factors.

Study I was a prospective multicentre study aiming to construct updated population-based references for fetal growth for the Swedish population from a cohort of 583 low-risk pregnancies. Comparisons were also made with other relevant growth charts.

In Study II, a population-based retrospective cohort study including 10 970 fresh ET, 6520 frozen ET, and 178 518 natural conception (NC) pregnancies, fetal growth after ART was explored with longitudinal statistics. Study III, a prospective longitudinal multicentre study of 82 fresh ET, 175 frozen ET and the 583 NC from Study I as reference, had similar aims. Fetuses after ART in general tended to be larger than NC in early pregnancy and thereafter growing at a slower rate than NC. This was more pronounced after fresh ET and at term mean fetal weight was lower than NC. Frozen ET remained heavier than NC in Study II but in Study III there were no significant differences.

Study IV was a population-based retrospective cohort study of 517 fresh ET, 284 frozen ET and  17 214 NC, examining growth from birth to five years of age. At birth, children after fresh ET were smaller, and those after frozen ET were larger than NC. Most differences were attenuated by 18 months of age.

The new references will in future studies be evaluated for the intended population. Our results support that there is a direct effect of ART on fetal growth. Although differences diminish with age, the differences in growth are known risk factors for future cardiometabolic disease.

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.

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.

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.