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Chapter: Obstetrics and Gynecology: Fetal Growth Abnormalities:Intrauterine Growth Restriction and Macrosomia

Intrauterine Growth Restriction: Etiology

IUGR is a descriptive term for a condition that has numerous potential causes. Determining the specific diagnosis is impor-tant for optimal management.

Etiology

 

IUGR is a descriptive term for a condition that has numerous potential causes. Determining the specific diagnosis is impor-tant for optimal management. Although a number of causes of IUGR have been recognized, a definite etiology of IUGR cannot be identified in approximately 50% of all cases. In addition, because the utilization of a percentile cut-off of 10% alone will result in a high proportion of false-positives, two-thirds or more of such fetuses categorized as IUGR will be simply constitutionally small and otherwise healthy.

 

Factors that affect fetal growth are extensive and include maternal, fetal, and placental causes; these are listed in Box 18.1.

 


MATERNAL FACTORS

 

Maternal factors include viral infections, such as rubella, varicella, and cytomegalovirus, which are associated with high rates of growth restriction, particularly if infection occurs early in pregnancy. Although these infections may manifest only as mild “flu-like” illnesses, injury to the fetus during organogenesis can result in a decreased cell number, resulting in diminished growth with or without multiple congenital anomalies. Five percent or fewer of all cases of IUGR are related to early infection with these or other viral agents. Maternal substance abuse affects fetal growth and almost all infants with fetal alcohol syn-drome will be growth-restricted. Women who smoke during pregnancy deliver babies 200 g smaller on average than do women who do not smoke; moreover, the rate of growth restriction is 3- to 4-fold greater among babies born to women who smoke during pregnancy. Women who use narcotics, heroin, methadone, or cocaine also have rates of growth-restricted babies ranging from as much as 30% to 50%. Medications known to be associ-ated with IUGR include anticonvulsant medications, warfarin, and folic acid antagonists. Altitude may also affect fetal growth.

 

Other maternal factors that affect fetal growth and body composition include demographic factors and med-ical conditions. Extremes in maternal age (age younger than 16 years and older than 35 years) are associated with an increased risk of fetal growth restriction. Medical conditions that alter or affect placental function may also be causative factors.

 

Although one common pathway has not been clearly identified, many of these disorders occur together. Women with a history of prior obstetric complications have an increased risk of growth abnormalities. Maternal metabo-lism and body composition are two of the strongest regula-tors of fetal growth. Nutritional deficiencies and inadequate weight gain, particularly in teens or in underweight women, may result in IUGR.

 

FETAL FACTORS

 

The inherent growth potential of the individual is deter-mined genetically. Female fetuses are at greater risk for IUGR than males. In addition, up to 20% of growth-restricted fetuses have a chromosomal abnormality. In addition, single-gene mutations such as the glucokinase gene mutation, or genetic syndromes such as Beckwith-Wiedemann syndrome can also result in abnormalities of growth. Finally, multifetal pregnancies are at increased risk for growth restriction.

 

PLACENTAL FACTORS

 

The placenta is critical for nutrient regulation and trans-portation from mother to fetus. Abnormalities in placenta-tion or defective trophoblast invasion and remodeling may contribute to fetal growth restriction as well as other dis-orders of pregnancy. In addition, uterine anomalies (uter-ine septum or fibroids) may limit placental implantation and development and, consequently, nutrient transport, result-ing in inadequate nutrition for the developing fetus. Finally, the genetic composition of the placenta is important and abnormalities such as confined placental mosaicism are asso-ciated with growth delay.


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