Risk factors and outcomes associated with first-trimester fetal growth restriction.
BACKGROUND
Adverse environmental exposures lead to developmental adaptations in fetal life. The influences of maternal physical characteristics and lifestyle habits on first-trimester fetal adaptations and the postnatal consequences are not known.


OBJECTIVE
To determine the risk factors and outcomes associated with first-trimester growth restriction.


METHODS
Prospective evaluation of the associations of maternal physical characteristics and lifestyle habits with first-trimester fetal crown to rump length in 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle. Subsequently, we assessed the associations of first-trimester fetal growth restriction with the risks of adverse birth outcomes and postnatal growth acceleration until the age of 2 years. The study was based in Rotterdam, The Netherlands. Mothers were enrolled between 2001 and 2005.


METHODS
First-trimester fetal growth was measured as fetal crown to rump length by ultrasound between the gestational age of 10 weeks 0 days and 13 weeks 6 days. Main birth outcomes were preterm birth (gestational age <37 weeks), low birth weight (<2500 g), and small size for gestational age (lowest fifth birth centile). Postnatal growth was measured until the age of 2 years.


RESULTS
In the multivariate analysis, maternal age was positively associated with first-trimester fetal crown to rump length (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 to 1.18 per standard deviation score increase). Higher diastolic blood pressure and higher hematocrit levels were associated with a shorter crown to rump length (differences, -0.40 mm; 95% CI, -0.74 to -0.06 and -0.52 mm; 95% CI, -0.90 to -0.14 per standard deviation increase, respectively). Compared with mothers who were nonsmokers and optimal users of folic acid supplements, those who both smoked and did not use folic acid supplements had shorter fetal crown to rump lengths (difference, -3.84 mm; 95% CI, -5.71 to -1.98). Compared with normal first-trimester fetal growth, first-trimester growth restriction was associated with increased risks of preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 to 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 to 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 to 4.25). Each standard deviation decrease in first-trimester fetal crown to rump length was associated with a postnatal growth acceleration until the age of 2 years (standard deviation score increase, 0.139 per 2 years; 95% CI, 0.097 to 0.181).


CONCLUSIONS
Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth. First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood.
The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
Dennis O
DO
Mook-Kanamori
Eric A P
EA
Steegers
Paul H
PH
Eilers
Hein
H
Raat
Albert
A
Hofman
Vincent W V
VW
Jaddoe
D000328:Adult; D001794:Blood Pressure; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000453:epidemiology*; D006400:Hematocrit; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008019:Life Style; D008423:Maternal Age; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D047928:Premature Birth; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D016216:Ultrasonography, Prenatal; D055815:Young Adult