Abstract
IMPORTANCE People conceived using assisted reproductive technology (ART) make up an
increasing proportion of the world’s population.
OBJECTIVE To investigate the association of ART conception with offspring growth and adiposity
from infancy to early adulthood in a large multicohort study.
DESIGN, SETTING, AND PARTICIPANTS This cohort study used a prespecified coordinated analysis
across 26 European, Asia-Pacific, and North American population-based cohort studies that included
people born between 1984 and 2018, with mean ages at assessment of growth and adiposity
outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and
February 2022.
EXPOSURES Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and
embryo transfer) vs natural conception (NC; without any medically assisted reproduction).
MAIN OUTCOMES AND MEASURES The main outcomes were length / height, weight, and body
mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort
was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and
ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13
age groups.
RESULTS Up to 158 066 offspring (4329 conceived by ART) were included in each age-group metaanalysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were
NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence,
with differences largest at the youngest ages and attenuating with older child age. For example,
adjusted mean differences in offspring weight were −0.27 (95% CI, −0.39 to −0.16) SD units at age
younger than 3 months, −0.16 (95% CI, −0.22 to −0.09) SD units at age 17 to 23 months, −0.07 (95%
CI, −0.10 to −0.04) SD units at age 6 to 9 years, and −0.02 (95% CI, −0.15 to 0.12) SD units at age 14
to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo
transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was −0.14
[95% CI, −0.20 to −0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, −0.15 to 0.15SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat
measurements, and there was imprecise evidence that offspring conceived by ART developed
greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17
years: 0.23 [95% CI, −0.04 to 0.50] SD units).
CONCLUSIONS AND RELEVANCE These findings suggest that people conceiving or conceived by
ART can be reassured that differences in early growth and adiposity are small and no longer evident
by late adolescence
increasing proportion of the world’s population.
OBJECTIVE To investigate the association of ART conception with offspring growth and adiposity
from infancy to early adulthood in a large multicohort study.
DESIGN, SETTING, AND PARTICIPANTS This cohort study used a prespecified coordinated analysis
across 26 European, Asia-Pacific, and North American population-based cohort studies that included
people born between 1984 and 2018, with mean ages at assessment of growth and adiposity
outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and
February 2022.
EXPOSURES Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and
embryo transfer) vs natural conception (NC; without any medically assisted reproduction).
MAIN OUTCOMES AND MEASURES The main outcomes were length / height, weight, and body
mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort
was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and
ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13
age groups.
RESULTS Up to 158 066 offspring (4329 conceived by ART) were included in each age-group metaanalysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were
NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence,
with differences largest at the youngest ages and attenuating with older child age. For example,
adjusted mean differences in offspring weight were −0.27 (95% CI, −0.39 to −0.16) SD units at age
younger than 3 months, −0.16 (95% CI, −0.22 to −0.09) SD units at age 17 to 23 months, −0.07 (95%
CI, −0.10 to −0.04) SD units at age 6 to 9 years, and −0.02 (95% CI, −0.15 to 0.12) SD units at age 14
to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo
transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was −0.14
[95% CI, −0.20 to −0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, −0.15 to 0.15SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat
measurements, and there was imprecise evidence that offspring conceived by ART developed
greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17
years: 0.23 [95% CI, −0.04 to 0.50] SD units).
CONCLUSIONS AND RELEVANCE These findings suggest that people conceiving or conceived by
ART can be reassured that differences in early growth and adiposity are small and no longer evident
by late adolescence
| Original language | English |
|---|---|
| Article number | e2222106 |
| Pages (from-to) | E2222106 |
| Number of pages | 16 |
| Journal | JAMA Network Open |
| Volume | 5 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 26 Jul 2022 |
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