First trimester origins of fetal growth impairment

doi:10.1053/j.semperi.2003.10.012

Seminars in Perinatology

Volume 28, Issue 1, February 2004, Pages 41-50

https://doi.org/10.1053/j.semperi.2003.10.012 Get rights and content

Abstract

The timing of factors that lead to disorders of fetal growth have been studied for many years. Previous studies have focused on disorders of the “second wave” of trophoblast invasion of myometrial arterioles and on fetal weight gain in the third trimester. Over the last 5 years, clinical studies have shown associations between first trimester ultrasound and biochemical parameters and the risk of later adverse perinatal outcome. First trimester growth restriction is associated with an increased risk of low birth weight, low birth weight percentile for gestational age and extremely preterm birth. This may reflect a defect in early pregnancy placentation and later adverse outcome. Consistent with this hypothesis, low first trimester circulating maternal concentrations of pregnancy-associated plasma protein A, a trophoblast-derived regulator of the insulin-like growth factor system, are associated with an increased risk of later stillbirth, growth restriction, pre-term birth and pre-eclampsia. Even among healthy women having normal pregnancies, first trimester circulating concentrations of pregnancy-associated plasma protein A correlate with the timing of spontaneous labor and the eventual birth weight. These analyses suggest that in some women complications of late pregnancy have their origins in the very earliest weeks of gestation and precede first attendance for prenatal care.

Section snippets

Early pregnancy assessment of growth

The major ultrasonic measure of fetal growth in early pregnancy is the crown rump length (CRL), which is conceptually self-explanatory and technically described elsewhere.2 Early fetal growth can be assessed by comparing the actual size of the embryo or fetus with the expected size on the basis of standard growth charts and the last menstrual period (LMP).5 Use of the LMP assumes ovulation occurs on day 14, where day 1 is the first day of the last menses. While this is true on average, the

Placental function in the first trimester

A detailed discussion of placental development in the first trimester of pregnancy is outside the scope of this review and many key aspects of this subject has previously been reviewed in detail.18, 19, 20 The key issue in the context of this review is the mechanism by which the fetus obtains nutrition at different stages of pregnancy. Since invasion of the decidua and myometrium is a feature of the first trimester in the human, it might be assumed that fetal nutrition in early pregnancy is

Biochemical and doppler interrogation of early placental function

There are several approaches which have interrogated the relationship between first trimester placentation and subsequent pregnancy outcome. First, the relationship between circulating concentrations of trophoblast derived proteins in early pregnancy and subsequent outcome has been studied. Second the predictive ability of first trimester Doppler assessment of uterine vascular resistance has been studied as a proxy for the effectiveness of early trophoblast invasion. Third, a number of studies

PAPP-A and free β human chorionic gonadotrophin

Large scale studies relating the outcome of pregnancy to maternal circulating concentrations of trophoblast derived proteins in the first trimester have tended to focus on biochemical assays employed in assessment of Down syndrome risk, specifically, pregnancy associated plasma protein A (PAPP-A) and the free β subunit of human chorionic gonadotrophin (FβhCG). Early studies of first trimester measurement of PAPP-A, FβhCG and perinatal outcome reported inconsistent results. One study compared

Other indicators of first trimester placental function

There are very few data on other circulating placentally derived proteins and later pregnancy complications. A single study reported higher levels of placenta growth factor in early pregnancy among fetuses which were ultimately delivered small for gestational age.40 However, ultrasound can also be used to assess early placental function. It has been shown that women with a uterine artery pulsatility index in the uppermost quartile at 12 to 13 weeks have a 4-fold risk of hypertensive disorders

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First trimester origins of fetal growth impairment

Abstract

Section snippets

Early pregnancy assessment of growth

Placental function in the first trimester

Biochemical and doppler interrogation of early placental function

PAPP-A and free β human chorionic gonadotrophin

Other indicators of first trimester placental function

Am J Clin Nutr

Am J Obstet Gynecol

Obste Gyneco

Early Hum Dev

Placenta

Placenta

Placenta

Am J Obstet Gynecol

Br J Obstet Gynaecol

Mol Cell Endocrinol

Obstet. Gynecol

Placenta

Am J Clin Nutr

Lancet

J Chron Dis

Am Heart J

Regulation of fetal growth

Clinical applications of ultrasonic fetal measurements

Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia5 year randomised controlled trial

BMJ

A critical evaluation of sonar “crown-rump length” measurements

Br J Obstet Gynaecol

The normal menstrual cycle

Ultrasound evidence for variability in the size and development of normal human embryos before the tenth post-insemination week after assisted reproductive technologies

Hum Reprod

Incidence and significance of unequal gestational sac diameter or embryo crown-rump length in twin pregnancy

Hum Reprod

First-trimester growth and the risk of low birth weight

N Engl J Med

First trimester growth and the risk of adverse pregnancy outcome

J Soc Gynecol Invest

Gestational age and induction of labour for prolonged pregnancy

Br J Obstet Gynaecol

Does a discrepancy between gestational age determined by biparietal diameter and last menstrual period sometimes signify early intrauterine growth retardation?

Br J Obstet Gynaecol

A discrepancy between gestational age estimated by last menstrual period and biparietal diameter may indicate an increased risk of fetal death and adverse pregnancy outcome

Br J Obstet Gynaecol

Adverse obstetric outcome in fetuses that are smaller than expected at second trimester routine ultrasound examination

Acta Obstet Gynecol Scand