ACOG2013 FGR
1122 VOL. 121, NO. 5, MAY 2013 OBSTETRICS & GYNECOLOGY
Background
Terminology
The terminology for classifying fetuses and newborns who have failed to achieve normal weight is inconsistent. Communication between obstetric and newborn practi-tioners is facilitated by the use of clearly defined terms that characterize fetal and newborn weight according to either the absolute weight or the weight percentile for a given gestational age (1–4). In this document, the term fetal growth restriction will be used to describe fetuses with an estimated fetal weight that is less than the 10th percentile for gestational age, whereas the term small for gestational age (SGA) will be used exclusively to describe newborns whose birth weight is less than the 10th percentile for gestational age.
Prevalence
The prevalence of fetal growth restriction depends on the definition used. As noted previously, the most widely used
definition of fetal growth restriction in the United States is an estimated fetal weight that is less than the 10th percentile for gestational age (5). However, this defini-tion does not take into account the individualized growth potential of each fetus, and its use may fail to identify larger fetuses that have not achieved their growth poten-tial and may be at risk of adverse outcomes. Conversely, this definition will result in the misdiagnosis of fetal growth restriction for some constitutionally small fetuses (6–9). In an attempt to assess more accurately whether newborns and fetuses are of appropriate growth, investi-gators have devised formulas for individualized growth standards (10, 11). H owever, use of such formulas has not been shown to improve outcomes.
Etiology
The etiology of fetal growth restriction can be broadly categorized into maternal, fetal, and placental (see Box 1). Although the primary pathophysiologic mechanisms underlying these conditions are different, they often (but
Committee on Practice Bulletins—Obstetrics. This Practice Bulletin was developed by the American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics and the Society for Maternal-Fetal Medicine Publications Committee with the assistance of Henry Galan, MD, and William Grobman, MD. The information is designed to aid practitioners in making decisions about appropriate obstetric and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.
PRACTICE BULLETIN
Fetal Growth Restriction
Fetal growth restriction, also known as intrauterine growth restriction, is a common complication of pregnancy that has been associated with a variety of adverse perinatal outcomes. There is a lack of consensus regarding terminol-ogy, etiology, and diagnostic criteria for fetal growth restriction, with uncertainty surrounding the optimal manage-ment and timing of delivery for the growth-restricted fetus. An additional challenge is the difficulty in differentiating between the fetus that is constitutionally small and fulfilling its growth potential and the small fetus that is not fulfilling its growth potential because of an underlying pathologic condition. The purpose of this document is to review the topic of fetal growth restriction with a focus on terminology, etiology, diagnostic and surveillance tools, and guidance for management and timing of delivery.
N UMBER 134, M AY 2013
(Replaces Practice Bulletin Number 12, January 2000)
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIAN –GYNECOLOGISTS
The American College of
Obstetricians and Gynecologists
WOMEN’S HEALTH CARE PHYSICIANS
Society for
Maternal-Fetal Medicine
Maternal Nutrition Array Longitudinal studies of women who conceived and gave
birth during famine periods have shown an associa-
tion between SGA and maternal malnutrition (26, 27).
In these studies, extremely poor protein intake before
26 weeks of gestation was associated with SGA, and
severe caloric restriction (ie, intake of 600–900 kcal
daily) was associated with modest reductions in birth
weight. H owever, there is no high-quality evidence to
suggest that additional nutrient intake in the absence
of true maternal malnutrition increases fetal weight or
improves the outcome in cases of suspected fetal growth
restriction (28).
Multiple Gestation
Although twin pregnancies account for only 2–3% of
live births in the United States, they account for 10–15%
of adverse neonatal outcomes and are associated with an
increased frequency of preterm births and SGA births
(29–31). The risk of SGA in multiple gestations has
been reported to be as high as 25% for twin pregnancies
and 60% for triplet and quadruplet pregnancies (32). In
addition, monochorionic twin pregnancies are at risk of
SGA because of unequal placental sharing and twin–
twin transfusion syndrome (33).
Teratogen Exposure
Exposure to certain maternal medications has been
associated with fetal growth restriction. The effect of
any particular medication is dependent on the inherent
teratogenicity of the drug, the timing and duration of
exposure, the dosage, and individual genetic predisposi-
tion for drug metabolism. Use of certain antineoplastic
medications (eg, cyclophosphamide), antiepileptic drugs
(eg, valproic acid), and antithrombotic drugs (eg, warfa-
rin), has been associated with an increased risk of fetal
growth restriction (34–38).
Infectious Diseases
It has been estimated that intrauterine infection may
be the primary etiology underlying approximately
5–10% of cases of fetal growth restriction (39). Malaria
accounts for most cases of infection-related fetal growth
restriction worldwide (40). Other infections implicated
as causes of fetal growth restriction include cytomega-
lovirus, rubella, toxoplasmosis, varicella, and syphilis
(39, 41–44).
Genetic and Structural Disorders
Fetal growth restriction is associated with certain chro-
mosomal abnormalities: at least 50% of fetuses with tri-
somy 13 or trisomy 18 have fetal growth restriction (45).
VOL. 121, NO. 5, MAY 2013Practice Bulletin Fetal Growth Restriction1123
Confined placental mosaicism that is identified by cho-rionic villus sampling also has been associated with fetal growth restriction (46, 47).
Fetuses with many types of structural malformations (but without chromosomal or genetic abnormalities) also have an increased risk of fetal growth restriction (48). For example, fetuses and newborns with congenital heart disease are at an increased risk of fetal growth restric-tion and SGA, respectively, compared with fetuses and newborns without these malformations (49, 50). Gastro-schisis is another malformation commonly associated with fetal growth restriction, which is present in up to 25% of cases of gastroschisis (51).
Placental Disorders and Umbilical Cord Abnormalities
Abnormal placentation that results in poor placental perfusion (ie, placental insufficiency) is the most com-mon pathology associated with fetal growth restriction (52). An association between fetal growth restriction and certain placental disorders (eg, abruption, infarction, circumvallate shape, hemangioma, and chorioangioma) and umbilical cord abnormalities (eg, velamentous or marginal cord insertion) also has been suggested (34, 53–57). H owever, other placental disorders, such as placenta accreta and placenta previa, have not been associated consistently with fetal growth restriction (58).
Approximately 1% of all pregnancies are compli-cated by the presence of a single umbilical artery (59). Identification of a single umbilical artery, in the absence of additional anatomical or chromosomal abnormalities, has been associated with fetal growth restriction in some studies but not in others (60, 61).
Perinatal Morbidity and Mortality
Fetal growth restriction increases the risks of intrauterine demise, neonatal morbidity, and neonatal death (62). Furthermore, epidemiologic studies have revealed that growth-restricted fetuses are predisposed to the devel-opment of cognitive delay in childhood and diseases in adulthood (eg, obesity, type 2 diabetes mellitus, coro-nary artery disease, and stroke) (63, 64).
Fetal growth restriction is associated with a signifi-cantly increased risk of stillbirth, with the most severely affected fetuses being at greatest risk (65). At fetal weights less than the 10th percentile for gestational age, the risk of fetal death is approximately 1.5%, which is twice the background rate of fetuses of normal growth. Comparatively, the risk of fetal death increases to 2.5% at fetal weights less than the 5th percentile for gesta-tional age (66, 67). Growth-restricted fetuses with absent or reversed end-diastolic flow of the umbilical artery are at particular increased risk of adverse outcomes and have an increased frequency of neonatal mortality and mor- bidity (68).
Small-for-gestational-age newborns are predisposed to complications, including hypoglycemia, hyperbiliru- binemia, hypothermia, intraventricular hemorrhage, nec-rotizing enterocolitis, seizures, sepsis, respiratory distress syndrome, and neonatal death (69–73).
Screening for Fetal Growth Restriction Physical Examination or History
Fundal height measured in centimeters (between 24–38 weeks of gestation) approximates the gestational age and is used to screen for fetal growth less than or greater than the 10th percentile (74). A single fundal height measure-ment at 32–34 weeks of gestation has been reported to be approximately 65–85% sensitive and 96% specific for detecting the growth-restricted fetus (75–79). Maternal obesity and uterine leiomyomas are factors that may limit the accuracy of fundal height measurement as a screening tool. If the accuracy of fundal height is com-promised because of such factors, ultrasonography may be a better screening modality.
Ultrasonographic Diagnosis and Evaluation To assess for fetal growth restriction, four biometric measures are commonly used: 1) biparietal diameter, 2) head circumference, 3) abdominal circumference, and 4) femur length. The biometric measurements can be combined to generate an estimated fetal weight (80). The estimate may deviate from the birth weight by up to 20% in 95% of cases, and for the remaining 5% of cases, the deviation is even greater than 20% (78, 81–83). If the ultrasonographically estimated fetal weight is below the 10th percentile for gestational age, further evaluation should be considered, such as amniotic fluid assess-ment and Doppler blood flow studies of the umbilical artery. Because growth-restricted fetuses have a high incidence of structural and genetic abnormalities, an ultrasonographic examination of fetal anatomy also is recommended if not performed already.
The utility of Doppler velocimetry evaluation, especially of the umbilical artery, has been studied and reviewed extensively in cases of fetal growth restric-tion (84). Absent or reversed end-diastolic flow in the umbilical artery is associated with an increased risk of perinatal mortality (85–88). The rate of perinatal death is reduced by as much as 29% when umbilical artery Doppler velocimetry is added to standard antepartum testing in the setting of fetal growth restriction (89, 90). Flow in the ductus venosus also has been measured in
1124 Practice Bulletin Fetal Growth Restriction OBSTETRICS & GYNECOLOGY
an attempt to assess fetal status, but its use has not been shown to improve outcomes (91–94).
Clinical Considerations and Recommendations
How should pregnancies be screened for
fetal growth restriction, and how is screening accomplished?
All pregnant patients should be screened for risk factors for fetal growth restriction through a review of medi-cal and obstetric history. Fundal height measurements should be performed at each prenatal care visit after 24 weeks of gestation. A discrepancy between weeks of gestational age and fundal height measurement of greater than 3 has been proposed for identifying a fetus that may be growth restricted (74). The practitioner should keep in mind the potential limitation of assess-ing fundal height in the presence of maternal obesity, multiple pregnancy, or a history of leiomyomas; in mul-tiple gestations or in cases where the fundus cannot be palpated, an ultrasound examination is preferred as a screening tool. Ultrasonographic screening also may be used in the presence of maternal factors that increase the risk of fetal growth restriction.
Although other approaches to fetal growth restric-tion screening have been studied (including universal third-trimester ultrasonography, uterine artery Doppler velocimetry, and measurement of analytes, such as preg-nancy-associated plasma protein A) there is no evidence that these fetal growth restriction screening methods improve outcomes (95–102).
How should women with a prior birth of
a small for gestational age newborn be
evaluated?
The risk of recurrence of an SGA birth is approximately 20% (9). Any patient with a prior birth of an SGA new-born should have her medical and obstetric histories reviewed to help identify any additional risk factors, particularly modifiable risk factors. In these women, it may be reasonable to perform serial ultrasonography for growth assessment, although the optimal surveillance regimen has not been determined. Maternal history of a prior SGA newborn with normal fetal growth in the current pregnancy is not an indication for antenatal fetal heart rate testing, biophysical profile testing, or umbili-cal artery Doppler velocimetry (103).
Other maternal risk factors for SGA have been evaluated. One criterion for the diagnosis of antiphos-pholipid syndrome includes a prior pregnancy affected by a morphologically normal growth-restricted fetus that required delivery before 34 weeks of gestation.
H owever, there is insufficient evidence that screening and treatment in a subsequent pregnancy improves out-come (104). H eterozygosity for the inherited thrombo-philias (eg, factor V Leiden mutation and prothrombin mutation) has not consistently been associated with fetal growth restriction, and maternal testing for these throm-bophilias is not indicated (17, 104).
Can fetal growth restriction be prevented?
A variety of approaches have been undertaken to prevent fetal growth restriction. Many nutritional and dietary supplemental strategies to prevent fetal growth restric-tion have been studied, although none has been effec-tive. These include individualized nutritional counseling (105); increased consumption of fish, low-fat meats, grains, fruits, and vegetables (106); consumption of a low-salt diet (107); supplementation with iron (108), zinc (109), calcium (110), protein (111), magnesium (112), and vitamin D (113). Therefore, nutritional and dietary supplemental strategies for the prevention of fetal growth restriction are not effective and are not recommended.
Similarly, there is no consistent evidence that either inpatient or outpatient bed rest prevents fetal growth restriction or reduces the incidence of SGA births (114). In women with a history of an SGA birth, some experts have advocated for the use of aspirin to prevent placen-tal insufficiency; however, there is insufficient evidence for such therapy to be routinely indicated for fetal growth restriction prevention (115–118).
When should genetic counseling and prena-
tal diagnostic testing be offered in the case of fetal growth restriction?
Although fetal growth restriction alone may be associ-ated with an aneuploid fetus, the risk of aneuploidy is increased if fetal structural abnormalities also are pres-ent. Thus, the combination of fetal growth restriction and a structural defect should prompt patient counseling about the type of anomaly and consideration of prenatal diagnostic testing. Also, because fetal growth restriction detected earlier in gestation is more commonly associ-ated with aneuploidy (119), midtrimester onset of fetal growth restriction is an indication to offer genetic coun-seling and prenatal diagnostic testing.
How should a pregnancy complicated by fetal
growth restriction be evaluated and managed? Ultrasonography remains the best method for eval-uating the growth-restricted fetus. Monitoring the
VOL. 121, NO. 5, MAY 2013Practice Bulletin Fetal Growth Restriction1125
1126 Practice Bulletin Fetal Growth Restriction OBSTETRICS & GYNECOLOGY
women may choose to forgo delivery of a severely growth-restricted fetus at 25 weeks of gestation even if there is an increased risk of fetal death. Management may be enhanced by an individualized and multidisci-plinary approach. When intervention for perinatal ben-efit is the preferred option, antenatal fetal surveillance may help guide the timing of delivery. Fetal growth restriction alone is not an indication for cesarean deliv-ery and the route of delivery should be based on other clinical circumstances.
The Growth Restriction Intervention Trial is cur-rently the only published randomized trial to assess the timing of delivery of the early preterm (less than 34 weeks of gestation) growth-restricted fetus. In this trial, women with growth-restricted fetuses whose obstetri-cians were uncertain whether delivery would be ben-eficial, were randomized to either the early delivery group (delivery within 48 hours) or to the expectant management group (with antepartum surveillance until it was felt that delivery should not be delayed any lon-ger). The rates of betamethasone administration were the same in both groups. Perinatal survival was similar, and at the 6–12-year follow-up there were no differ-ences in cognitive, language, behavior, or motor abili-ties of the children born to women in the early-delivery group versus those in the expectant management group (131–133). In the Disproportionate Intrauterine Growth Intervention Trial at Term, women with singleton gesta-tions at or beyond 36 weeks with suspected fetal growth restriction (defined as an estimated fetal weight less than the 10th percentile) were randomized to undergo delivery or expectant management with delivery only if some other indication arose (134). There were no differ-ences in composite neonatal outcome between these two groups, although the study cohort was not large enough to determine whether individual outcomes, such as peri-natal death, were affected by the different management approaches.
No adequately powered randomized trials have been performed to determine the optimal time for delivery of the growth-restricted fetus between 34 weeks and 36 weeks of gestation. Based on existing data regarding timing of delivery as well as expert consensus, a joint conference of the Eunice Kennedy Shriver National Institute of Child H ealth and H uman Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists suggested the following two timing strategies when fetal growth restriction has been diagnosed: 1) delivery at 38 0/7–39 6/7 weeks of gestation in cases of isolated fetal growth restriction and 2) delivery at 34 0/7–37 6/7 weeks of gestation in cases of fetal growth restriction with additional risk factors for adverse
growth-restricted fetus includes serial ultrasonographic measurements of fetal biometry and amniotic fluid vol-ume. Antenatal surveillance with umbilical artery Doppler velocimetry and antepartum testing (eg, nonstress tests or biophysical profiles) should not begin before a gestational age when delivery would be considered for perinatal benefit (30, 31, 120–124). The optimal interval for fetal growth assessment and the optimal surveillance regimen have not been established. Most growth-restricted fetuses can be adequately evaluated with serial ultrasonography every 3–4 weeks; ultrasound assessment of growth should not be performed more frequently than every 2 weeks because the inherent error associated with ultrasono- graphic measurements can preclude an accurate assess-ment of interval growth (125, 126).
What is the role of Doppler velocimetry in evaluating a pregnancy complicated by fetal growth restriction?
Umbilical artery Doppler velocimetry plays an impor-tant role in the management of a pregnancy complicated by a diagnosis of fetal growth restriction. Its use, in conjunction with standard fetal surveillance, such as nonstress tests, biophysical profiles, or both, is associ-ated with improved outcomes in fetuses in which fetal growth restriction has been diagnosed (90). Doppler assessment may provide insight into the etiology of fetal growth restriction because increased impedance in the umbilical artery suggests that the pregnancy is compli-cated by underlying placental insufficiency. Also, absent or reversed end-diastolic flow in the umbilical artery is associated with an increased frequency of perinatal mortality (86–88, 127) and can affect decisions regard-ing timing of delivery in the context of fetal growth restriction (84). Investigation of other fetal blood ves-sels with Doppler velocimetry, including assessments of the middle cerebral artery and the precordial venous system, has been explored in the setting of fetal growth restriction. However, these flow measurements have not been shown to improve perinatal outcome, and the role of these measures in clinical practice remains uncertain (91, 92, 127, 128–130).
When should a growth-restricted fetus be delivered?
The optimal timing of delivery of the growth-restricted fetus depends on the underlying etiology of the growth restriction (if known) as well as the estimated gesta-tional age. For example, altering the timing of delivery for fetuses with aneuploidy or congenital infection may not improve the outcome. Furthermore, in some cases patients may elect nonintervention. For example, some
outcome (eg, oligohydramnios, abnormal umbilical artery Doppler velocimetry results, maternal risk factors, or co-morbidities) (135).
When delivery for fetal growth restriction is antici-pated before 34 weeks of gestation, the delivery should be planned at a center with a neonatal intensive care unit and, ideally, after consultation with a maternal–fetal specialist. Antenatal corticosteroids should be adminis-tered before delivery because they are associated with improved preterm neonatal outcomes (136–138). For cases in which delivery occurs before 32 weeks of ges-tation, magnesium sulfate should be considered for fetal and neonatal neuroprotection in accordance with one of the accepted published protocols (139–142). Summary of Recommendations and Conclusions
The following recommendations and conclusions are based on good and consistent scientific evi-dence (Level A):
Umbilical artery Doppler velocimetry used in con-
junction with standard fetal surveillance, such as nonstress tests, or biophysical profiles, or both, is associated with improved outcomes in fetuses in which fetal growth restriction has been diagnosed.
When delivery for fetal growth restriction is antici-
pated before 34 weeks of gestation, antenatal corti-
costeroids should be administered before delivery because they are associated with improved preterm neonatal outcomes.
For cases in which delivery occurs before 32 weeks of gestation, magnesium sulfate should be consid-
ered for fetal and neonatal neuroprotection.
Nutritional and dietary supplemental strategies for the prevention of fetal growth restriction are not effective and are not recommended.
The following recommendations and conclusions are based primarily on consensus and expert opin-ion (Level C):
Fetal growth restriction alone is not an indication for cesarean delivery.
The optimal timing of delivery of the growth-
restricted fetus depends on the underlying etiology of the growth restriction (if known) as well as the estimated gestational age.Proposed Performance Measure
Percentage of pregnant women with suspected fetal growth restriction in whom a plan for assessment and surveillance of fetal growth and well-being is initiated, if delivery is not pursued at the time of diagnosis
References
1. Dunn PM. The search for perinatal definitions and
standards. Acta Paediatr Scand Suppl 1985;319:7–16.
(Level III) [PubMed]A
2. World Health Organization. Report of a scientific group
on health statistics methodology related to perinatal events. Document ICD/PE/74.4:1. Geneva: WHO; 1974.
(Level III) A
3. H offman H J, Stark CR, Lundin FE Jr, Ashbrook JD.
Analysis of birth weight, gestational age, and fetal viabil-
ity, U. S. births, 1968. Obstet Gynecol Surv 1974;29: 651–81. (Level II-3) [PubMed]A
4. Battaglia FC, Lubchenco LO. A practical classification of
newborn infants by weight and gestational age. J Pediatr
1967;71:159–63. (Level III) [PubMed]A
5. Beckmann CR, Ling FW, Barzansky BM, Herbert WN,
Laube DW, Smith RP. Obstetrics and gynecology. 6th ed.
Baltimore (MD): Lippincott Williams & Wilkins; 2010.
(Level III) A
6. Galan HL. Timing delivery of the growth-restricted fetus.
Semin Perinatol 2011;35:262–9. (Level III) [PubMed]
[Full Text]A
7. Platz E, Newman R. Diagnosis of IUGR: traditional
biometry. Semin Perinatol 2008;32:140–7. (Level III) [PubMed] [Full Text]A
8. Xu H, Simonet F, Luo ZC. Optimal birth weight percentile
cut-offs in defining small- or large-for-gestational-age.
Acta Paediatr 2010;99:550–5. (Level II-3) [PubMed]A 9. Ananth CV, Vintzileos AM. Distinguishing pathologi-
cal from constitutional small for gestational age births in population-based studies. Early H um Dev 2009;85: 653–8. (Level II-3) [PubMed][Full Text]A
10. Bukowski R, Uchida T, Smith GC, Malone FD, Ball RH,
Nyberg DA, et al. Individualized norms of optimal fetal
growth: fetal growth potential. First and Second Trimes-
ter Evaluation of Risk (FASTER) Research Consortium.
Obstet Gynecol 2008;111:1065–76. (Level II-2) [PubMed]
[Obstetrics & Gynecology]A
11. Gardosi J, Mul T, Mongelli M, Fagan D. Analysis of
birthweight and gestational age in antepartum stillbirths.
Br J Obstet Gynaecol 1998;105:524–30. (Level III) [PubMed]A
12. Ounsted M, Moar VA, Scott A. Risk factors associ-
ated with small-for-dates and large-for-dates infants. Br J
Obstet Gynaecol 1985;92:226–32. (Level II-3) [PubMed]
A
VOL. 121, NO. 5, MAY 2013Practice Bulletin Fetal Growth Restriction1127
13. Cunningham FG, Cox SM, H arstad TW, Mason RA,
Pritchard JA. Chronic renal disease and pregnancy out-
come. Am J Obstet Gynecol 1990;163:453–9. (Level III)
[PubMed]A
14. Duvekot JJ, Cheriex EC, Pieters FA, Menheere PP,
Schouten HJ, Peeters LL. Maternal volume homeostasis
in early pregnancy in relation to fetal growth restriction.
Obstet Gynecol 1995;85:361–7. (Level III) [PubMed]
[Obstetrics & Gynecology]A
15. Antiphospholipid syndrome. Practice Bulletin No. 132.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2012;120:1514–21. (Level III) [PubMed]
[Obstetrics & Gynecology]A
16. Facco F, You W, Grobman W. Genetic thrombophilias and
intrauterine growth restriction: a meta-analysis. Obstet Gynecol 2009;113:1206–16. (Level III) [PubMed]
[Obstetrics & Gynecology]A
17. Said JM, H iggins JR, Moses EK, Walker SP, Borg AJ,
Monagle PT, et al. Inherited thrombophilia polymor-
phisms and pregnancy outcomes in nulliparous women.
Obstet Gynecol 2010;115:5–13. (Level II-2) [PubMed]
[Obstetrics & Gynecology]A
18. Silver RM, Zhao Y, Spong CY, Sibai B, Wendel G Jr,
Wenstrom K, et al. Prothrombin gene G20210A muta-
tion and obstetric complications. Eunice Kennedy Shriver National Institute of Child H ealth and H uman Development Maternal–Fetal Medicine Units (NICH D MFMU) Network. Obstet Gynecol 2010;115:14–20.
(Level II-2) [PubMed][Obstetrics & Gynecology]A
19. Bada H S, Das A, Bauer CR, Shankaran S, Lester BM,
Gard CC, et al. Low birth weight and preterm births: etiologic fraction attributable to prenatal drug exposure.
J Perinatol 2005;25:631–7. (Level II-3) [PubMed][Full
Text]A
20. Shu XO, H atch MC, Mills J, Clemens J, Susser M.
Maternal smoking, alcohol drinking, caffeine consump-
tion, and fetal growth: results from a prospective study.
Epidemiology 1995;6:115–20. (Level II-2) [PubMed]A 21. Mills JL, Graubard BI, Harley EE, Rhoads GG, Berendes
HW. Maternal alcohol consumption and birth weight. How
much drinking during pregnancy is safe? JAMA 1984;
252:1875–9. (Level II-2) [PubMed]A
22. Virji SK. The relationship between alcohol consumption
during pregnancy and infant birthweight. An epidemio-
logic study. Acta Obstet Gynecol Scand 1991;70:303–8.
(Level II-3) [PubMed]A
23. Naeye RL, Blanc W, Leblanc W, Khatamee MA. Fetal
complications of maternal heroin addiction: abnormal growth, infections, and episodes of stress. J Pediatr 1973;
83:1055–61. (Level III) [PubMed]A
24. Fulroth R, Phillips B, Durand DJ. Perinatal outcome of
infants exposed to cocaine and/or heroin in utero. Am J
Dis Child 1989;143:905–10. (Level II-3) [PubMed] A 25. Little BB, Snell LM, Klein VR, Gilstrap LC 3rd. Cocaine
abuse during pregnancy: maternal and fetal implications.
Obstet Gynecol 1989;73:157–60. (Level II-3) [PubMed]
[Obstetrics & Gynecology]A
26. Antonov AN. Children born during the siege of Leningrad
in 1942. J Pediatr 1947;30:250–9. (Level III) [PubMed]
A
27. Smith CA. Effects of maternal under nutrition upon the
newborn infant in Holland (1944–1945). J Pediatr 1947;
30:229–43. (Level III) [PubMed]A
28. Say L, Gulmezoglu AM, Hofmeyr GJ. Maternal nutrient
supplementation for suspected impaired fetal growth.
Cochrane Database of Systematic Reviews 2003, Issue 1.
Art. No.: CD000148. DOI: 10.1002/14651858.CD000148.
(Meta-analysis) [PubMed] [Full Text]A
29. Guyer B, MacDorman MF, Martin JA, Peters KD,
Strobino DM. Annual summary of vital statistics-1997.
Pediatrics 1998;102:1333–49. (Level III) [PubMed][Full
Text]A
30. Powers WF, Kiely JL. The risks confronting twins: a
national perspective. Am J Obstet Gynecol 1994;170: 456–61. (Level II-3) [PubMed]A
31. H oulton MC, Marivate M, Philpott RH. The prediction
of fetal growth retardation in twin pregnancy. Br J Obstet
Gynaecol 1981;88:264–73. (Level II-3) [PubMed]A
32. Mauldin JG, Newman RB. Neurologic morbidity asso-
ciated with multiple gestation. Female Patient 1998;
23(4):27–46. (Level III) A
33. Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM.
Placental angioarchitecture in monochorionic twin preg-
nancies: relationship to fetal growth, fetofetal transfusion
syndrome, and pregnancy outcome. Am J Obstet Gynecol
2000;182:417–26. (Level III) [PubMed]A
34. Maulik D. Fetal growth restriction: the etiology. Clin
Obstet Gynecol 2006;49:228–35. (Level III) [PubMed]A 35. Battino D, Granata T, Binelli S, Caccamo ML, Canevini
MP, Canger R, et al. Intrauterine growth in the offspring
of epileptic mothers. Acta Neurol Scand 1992;86:555–7.
(Level III) [PubMed]A
36. Mastroiacovo P, Bertollini R, Licata D. Fetal growth in
the offspring of epileptic women: results of an Italian multicentric cohort study. Acta Neurol Scand 1988;78: 110–4. (Level II-2) [PubMed]A
37. Aviles A, Diaz-Maqueo JC, Talavera A, Guzman R,
Garcia EL. Growth and development of children of moth-
ers treated with chemotherapy during pregnancy: current
status of 43 children. Am J H ematol 1991;36:243–8.
(Level III) [PubMed]A
38. H all JG, Pauli RM, Wilson KM. Maternal and fetal
sequelae of anticoagulation during pregnancy. Am J Med
1980;68:122–40. (Level III) [PubMed]A
39. Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR,
editors. Creasy and Resnik’s maternal–fetal medicine: principles and practice. 6th ed. Philadelphia (PA): Saunders Elsevier; 2009. (Level III) A
40. Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K,
Brabin B, et al. Epidemiology and burden of malaria in
pregnancy. Lancet Infect Dis 2007;7:93–104. (Level III)
[PubMed]A
41. Donner C, Liesnard C, Content J, Busine A, Aderca J,
Rodesch F. Prenatal diagnosis of 52 pregnancies at risk
1128 Practice Bulletin Fetal Growth Restriction OBSTETRICS & GYNECOLOGY
VOL. 121, NO. 5, MAY 2013 Practice Bulletin Fetal Growth Restriction 1129
Obstet Gynecol Scand 1994;73:529–34. (Level III) [PubMed] A
54. Shanklin DR. The influence of placental lesions on the
newborn infant. Pediatr Clin North Am 1970;17:25–42. (Level II-3) [PubMed] A 55. Ananth CV, Demissie K, Smulian JC, Vintzileos AM.
Relationship among placenta previa, fetal growth restriction, and preterm delivery: a population-based study. Obstet Gynecol 2001;98:299–306. (Level II-3) [PubMed] [Obstetrics & Gynecology ] A 56. Ananth CV, Wilcox AJ. Placental abruption and peri-natal mortality in the United States. Am J Epidemiol 2001;153:332–7. (Level II-3) [PubMed] [Full Text] A 57. Chapman MG, Furness ET, Jones WR, Sheat JH. Sig-nificance of the ultrasound location of placental site in early pregnancy. Br J Obstet Gynaecol 1979;86:846–8. (Level III) [PubMed] A 58. Harper LM, Odibo AO, Macones GA, Crane JP, Cahill
AG. Effect of placenta previa on fetal growth. Am J Obstet Gynecol 2010;203:330.e1,330.e5. (Level II-2) [PubMed] [Full Text] A 59. Pollack RN, Divon MY. Intrauterine growth retarda-tion: definition, classification, and etiology. Clin Obstet Gynecol 1992;35:99–107. (Level III) [PubMed] A 60. Thummala MR, Raju TN, Langenberg P. Isolated single
umbilical artery anomaly and the risk for congenital malformations: a meta-analysis. J Pediatr Surg 1998;33: 580–5. (Meta-Analysis) [PubMed] A 61. Heifetz SA. Single umbilical artery. A statistical analysis
of 237 autopsy cases and review of the literature. Perspect Pediatr Pathol 1984;8:345–78. (Level III) [PubMed] A 62. Resnik R. Intrauterine growth restriction. Obstet Gynecol
2002;99:490–6. (Level III) [PubMed] [Obstetrics & Gynecology ] A 63. Pallotto EK, Kilbride H W. Perinatal outcome and later
implications of intrauterine growth restriction. Clin Obstet Gynecol 2006;49:257–69. (Level III) [PubMed] A 64. Barker DJ. Adult consequences of fetal growth restric-tion. Clin Obstet Gynecol 2006;49:270–83. (Level III) [PubMed] A 65. Clausson B, Cnattingius S, Axelsson O. Outcomes of post-
term births: the role of fetal growth restriction and mal-formations. Obstet Gynecol 1999;94:758–62. (Level II-3) [PubMed] [Obstetrics & Gynecology ] A 66. Getahun D, Ananth CV, Kinzler WL. Risk factors for
antepartum and intrapartum stillbirth: a population-based study. Am J Obstet Gynecol 2007;196:499–507. (Level II-3) [PubMed] [Full Text] A 67. Ego A, Subtil D, Grange G, Thiebaugeorges O, Senat MV,
Vayssiere C, et al. Customized versus population-based birth weight standards for identifying growth restrict-ed infants: a French multicenter study. Am J Obstet Gynecol 2006;194:1042–9. (Level II-3) [PubMed] [Full Text] A 68. Vergani P, Roncaglia N, Locatelli A, Andreotti C, Crippa I,
Pezzullo JC, et al. Antenatal predictors of neonatal out-come in fetal growth restriction with absent end-diastolic
for congenital cytomegalovirus infection. Obstet Gyne-col 1993;82:481–6. (Level III) [PubMed] [Obstetrics & Gynecology ] A
42. Lambert JS, Watts DH, Mofenson L, Stiehm ER, Harris
DR, Bethel J, et al. Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team. Aids 2000;14:1389–99. (Level I) [PubMed] A 43. Cailhol J, Jourdain G, Coeur SL, Traisathit P, Boonrod
K, Prommas S, et al. Association of low CD4 cell count and intrauterine growth retardation in Thailand. Perinatal H IV Prevention Trial Group. J Acquir Immune Defic Syndr 2009;50:409–13. (Level I) [PubMed] A 44. Iqbal SN, Kriebs J, H arman C, Alger L, Kopelman J,
Turan O, et al. Predictors of fetal growth in maternal HIV disease. Am J Perinatol 2010;27:517–23. (Level II-3) [PubMed] [Full Text] A 45. Eydoux P, Choiset A, Le Porrier N, Thepot F, Szpiro-Tapia S, Alliet J, et al. Chromosomal prenatal diagnosis: study of 936 cases of intrauterine abnormalities after ultrasound assessment. Prenat Diagn 1989;9:255–69. (Level III) [PubMed] A 46. Wolstenholme J, Rooney DE, Davison EV. Confined
placental mosaicism, IUGR, and adverse pregnancy out- come: a controlled retrospective U.K. collaborative survey. Prenat Diagn 1994;14:345–61. (Level II-2) [PubMed] A 47. Wilkins-H aug L, Roberts DJ, Morton CC. Confined
placental mosaicism and intrauterine growth retardation: a case-control analysis of placentas at delivery. Am J Obstet Gynecol 1995;172:44–50. (Level III) [PubMed] [Full Text] A 48. Khoury MJ, Erickson JD, Cordero JF, McCarthy BJ.
Congenital malformations and intrauterine growth retar-dation: a population study. Pediatrics 1988;82:83–90. (Level II-3) [PubMed] A 49. Wallenstein MB, H arper LM, Odibo AO, Roehl KA,
Longman RE, Macones GA, et al. Fetal congenital heart disease and intrauterine growth restriction: a ret-rospective cohort study. J Matern Fetal Neonatal Med 2012;25:662–5. (Level II-3) [PubMed] [Full Text] A 50. Malik S, Cleves MA, Zhao W, Correa A, H obbs CA.
Association between congenital heart defects and small for gestational age. National Birth Defects Prevention Study. Pediatrics 2007;119:e976–82. (Level II-3) [PubMed][Full Text] A 51. Raynor BD, Richards D. Growth retardation in fetuses
with gastroschisis. J Ultrasound Med 1997;16:13–6. (Level III) [PubMed] A 52. Salafia CM, Minior VK, Pezzullo JC, Popek EJ,
Rosenkrantz TS, Vintzileos AM. Intrauterine growth restriction in infants of less than thirty-two weeks’ ges-tation: associated placental pathologic features. Am J Obstet Gynecol 1995;173:1049–57. (Level II-3) [PubMed] [Full Text] A 53. Laurini R, Laurin J, Marsal K. Placental histology and
fetal blood flow in intrauterine growth retardation. Acta
1130 Practice Bulletin Fetal Growth Restriction OBSTETRICS & GYNECOLOGY
femur length in addition to head and abdomen mea-surements. Radiology 1984;150:535–40. (Level III) [PubMed] A
82. Chien PF, Owen P, Khan KS. Validity of ultrasound esti-mation of fetal weight. Obstet Gynecol 2000;95:856–60. (Level II-2) [PubMed] [Obstetrics & Gynecology ] A 83. Dudley NJ. A systematic review of the ultrasound esti-mation of fetal weight. Ultrasound Obstet Gynecol 2005; 25:80–9. (Level III) [PubMed] [Full Text] A 84. Berkley E, Chauhan SP, Abuhamad A. Doppler assess-ment of the fetus with intrauterine growth restric-tion. Society for Maternal–Fetal Medicine Publications Committee [published erratum appears in Am J Obstet Gynecol 2012;206:508]. Am J Obstet Gynecol 2012; 206:300–8. (Level III) [PubMed] [Full Text] A 85. Kingdom JC, Burrell SJ, Kaufmann P. Pathology and clin-ical implications of abnormal umbilical artery Doppler waveforms. Ultrasound Obstet Gynecol 1997;9:271–86. (Level III) [PubMed] [Full Text] A 86. Pardi G, Cetin I, Marconi AM, Lanfranchi A, Bozzetti P,
Ferrazzi E, et al. Diagnostic value of blood sampling in fetuses with growth retardation. N Engl J Med 1993; 328:692–6. (Level III) [PubMed] [Full Text] A 87. Nicolaides KH, Bilardo CM, Soothill PW, Campbell S.
Absence of end diastolic frequencies in umbilical artery: a sign of fetal hypoxia and acidosis. BMJ 1988; 297:1026–7. (Level III) [PubMed] [Full Text] A 88. Bilardo CM, Nicolaides KH, Campbell S. Doppler mea-surements of fetal and uteroplacental circulations: rela-tionship with umbilical venous blood gases measured at cordocentesis. Am J Obstet Gynecol 1990;162:115–20. (Level III) [PubMed] A 89. Giles W, Bisits A. Clinical use of Doppler ultrasound in
pregnancy: information from six randomised trials. Fetal Diagn Ther 1993;8:247–55. (Level III) [PubMed] A 90. Alfirevic Z, Stampalija T, Gyte GML. Fetal and umbili-cal Doppler ultrasound in normal pregnancy. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001450. DOI: 10.1002/14651858.CD001450.pub3. (Meta-analysis) [PubMed] [Full Text] A 91. Rizzo G, Capponi A, Arduini D, Romanini C. The value
of fetal arterial, cardiac and venous flows in predicting pH and blood gases measured in umbilical blood at cordo-centesis in growth retarded fetuses. Br J Obstet Gynaecol 1995;102:963–9. (Level III) [PubMed] A 92. Hecher K, Snijders R, Campbell S, Nicolaides K. Fetal
venous, intracardiac, and arterial blood flow measure-ments in intrauterine growth retardation: relationship with fetal blood gases. Am J Obstet Gynecol 1995;173:10–5. (Level III) [PubMed] [Full Text] A 93. Baschat AA. Doppler application in the delivery timing
of the preterm growth-restricted fetus: another step in the right direction. Ultrasound Obstet Gynecol 2004;23: 111–8. (Level III) [PubMed] [Full Text] A 94. Ghidini A. Doppler of the ductus venosus in severe
preterm fetal growth restriction: a test in search of a purpose? Obstet Gynecol 2007;109:250–2. (Level III) [PubMed] [Obstetrics & Gynecology ] A
flow in the umbilical artery. Am J Obstet Gynecol 2005; 193:1213–8. (Level II-3) [PubMed] [Full Text] A 69. McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth
weight in relation to morbidity and mortality among new-born infants. N Engl J Med 1999;340:1234–8. (Level II-2) [PubMed] [Full Text] A 70. Hartung J, Kalache KD, Heyna C, Heling KS, Kuhlig M,
Wauer R, et al. Outcome of 60 neonates who had ARED flow prenatally compared with a matched control group of appropriate-for-gestational age preterm neonates. Ultrasound Obstet Gynecol 2005;25:566–72. (Level II-2) [PubMed] [Full Text] A 71. Shand AW, H ornbuckle J, Nathan E, Dickinson JE,
French NP. Small for gestational age preterm infants and relationship of abnormal umbilical artery Doppler blood flow to perinatal mortality and neurodevelopmental outcomes. Aust N Z J Obstet Gynaecol 2009;49:52–8. (Level II-2) [PubMed] [Full Text] A 72. Jones RA, Roberton NR. Problems of the small-for-dates
baby. Clin Obstet Gynaecol 1984;11:499–524. (Level III) [PubMed] A 73. Alkalay AL, Graham JM Jr, Pomerance JJ. Evaluation
of neonates born with intrauterine growth retardation: review and practice guidelines. J Perinatol 1998;18:1 42–51. (Level III) [PubMed] A 74. Knox AJ, Sadler L, Pattison NS, Mantell CD, Mullins P.
An obstetric scoring system: its development and appli-cation in obstetric management. Obstet Gynecol 1993; 81:195–9. (Level II-3) [PubMed] [Obstetrics & Gyne-cology ] A 75. Leeson S, Aziz N. Customised fetal growth assess-ment. Br J Obstet Gynaecol 1997;104:648–51. (Level III) [PubMed] A 76. Jahn A, Razum O, Berle P. Routine screening for intra-uterine growth retardation in Germany: low sensitivity and questionable benefit for diagnosed cases. Acta Obstet Gynecol Scand 1998;77:643–8. (Level II-3) [PubMed] [Full Text] A 77. Kean LH, Liu DT. Antenatal care as a screening tool for
the detection of small for gestational age babies in the low risk population. J Obstet Gynaecol 1996;16:77–82. (Level II-3) A 78. Sparks TN, Cheng YW, McLaughlin B, Esakoff TF,
Caughey AB. Fundal height: a useful screening tool for fetal growth? J Matern Fetal Neonatal Med 2011;24: 708–12. (Level II-2) [PubMed] [Full Text] A 79. Goetzinger KR, Tuuli MG, Odibo AO, Roehl KA,
Macones GA, Cahill AG. Screening for fetal growth dis-orders by clinical exam in the era of obesity. J Perinatol 2012; DOI: 10.1038/jp.2012.130; 10.1038/jp.2012.130. (Level II-2) [PubMed] A 80. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK.
Estimation of fetal weight with the use of head, body, and femur measurements––a prospective study. Am J Obstet Gynecol 1985;151:333–7. (Level III) [PubMed] A 81. Hadlock FP, Harrist RB, Carpenter RJ, Deter RL, Park SK.
Sonographic estimation of fetal weight. The value of
VOL. 121, NO. 5, MAY 2013 Practice Bulletin Fetal Growth Restriction 1131
and neonatal lipids, and pregnancy outcome: a ran-domized clinical trial. Am J Obstet Gynecol 2005;193: 1292–301. (Level I) [PubMed] [Full Text] A
107. Steegers EA, Van Lakwijk HP, Jongsma HW, Fast JH,
De Boo T, Eskes TK, et al. (Patho)physiological impli-cations of chronic dietary sodium restriction during pregnancy; a longitudinal prospective randomized study. Br J Obstet Gynaecol 1991;98:980–7. (Level I) [Pub Med] A 108. Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE.
Daily oral iron supplementation during pregnancy. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD004736. DOI: 10.1002/14651858.CD0 04736.pub4. (Level III) [PubMed] [Full Text] A 109. Mori R, Ota E, Middleton P, Tobe-Gai R, Mahomed K,
Bhutta ZA. Zinc supplementation for improving preg- nancy and infant outcome. Cochrane Database of System-atic Reviews 2012, Issue 7. Art. No.: CD000230. DOI: 10. 1002/14651858.CD000230.pub4. (Meta-analysis) [PubMed] [Full Text] A 110. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L. Calcium
supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001059. DOI: 10.1002/14651858.CD001059.pub3. (Meta-analysis) [PubMed] [Full Text] A 111. Ota E, Tobe-Gai R, Mori R, Farrar D. Antenatal
dietary advice and supplementation to increase energy and protein intake. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD000032. DOI: 10.1002/14651858.CD000032.pub2. (Meta-analysis) [PubMed] [Full Text] A 112. Makrides M, Crowther CA. Magnesium supplementa-
tion in pregnancy. Cochrane Database of Systematic Reviews 2001, I ssue 4. A rt. N o.: C D000937. D OI: 10.1002/ 14651858.CD000937. (Meta-analysis) [PubMed] [Full Text] A 113. De-Regil LM, Palacios C, Ansary A, Kulier R, Pena-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008873. DOI: 10.1002/14651 858.CD008873.pub2. (Meta-analysis) [PubMed] [Full Text] A 114. Say L, Gulmezoglu AM, H ofmeyr GJ. Bed rest in
hospital for suspected impaired fetal growth. Cochrane Database of Systematic Reviews 1996, Issue 1. Art. No.: CD000034. DOI: 10.1002/14651858.CD000034. (Meta-analysis) [PubMed] [Full Text] A 115. Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F,
Marcoux S, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010; 116:402–14. (Meta-analysis) [PubMed] [Obstetrics & Gynecology ] A 116. Peleg D, Kennedy CM, Hunter SK. Intrauterine growth
restriction: identification and management. Am Fam Physician 1998;58:453–60, 466–7. (Level III) [PubMed] [Full Text] A
95. Irwin JC, Suen LF, Martina NA, Mark SP, Giudice LC.
Role of the IGF system in trophoblast invasion and pre-eclampsia. H um Reprod 1999;14(suppl 2):90–6. (Level III) [PubMed] A 96. Spencer K, Cowans NJ, Avgidou K, Molina F, Nicolaides
KH. First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2008;31:15–9. (Level II-3) [PubMed] [Full Text] A 97. Krantz D, Goetzl L, Simpson JL, Thom E, Zachary J,
Hallahan TW, et al. Association of extreme first-trimes-ter free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes. First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group. Am J Obstet Gynecol 2004;191: 1452–8. (Level II-2) [PubMed] [Full Text] A 98. Goetzl L, Krantz D, Simpson JL, Silver RK, Zachary JM,
Pergament E, et al. Pregnancy-associated plasma protein A, free beta-hCG, nuchal translucency, and risk of preg-nancy loss. Obstet Gynecol 2004;104:30–6. (Level II-2) [PubMed] [Obstetrics & Gynecology ] A 99. Dugoff L. First- and second-trimester maternal serum
markers for aneuploidy and adverse obstetric outcomes.Society for Maternal-Fetal Medicine. Obstet Gynecol 2010;115:1052–61. (Level II-2) [PubMed] [Obstetrics & Gynecology ] A
100. Zhong Y, Tuuli M, Odibo AO. First-trimester assessment of placenta function and the prediction of preeclamp-sia and intrauterine growth restriction. Prenat Diagn 2010;30:293–308. (Level III) [PubMed] [Full Text] A
101. Poon LC, Stratieva V, Piras S, Piri S, Nicolaides KH. Hypertensive disorders in pregnancy: combined screen-ing by uterine artery Doppler, blood pressure and serum PAPP-A at 11–13 weeks. Prenat Diagn 2010;30:216–23. (Level II-2) [PubMed] [Full Text] A 102. Goetzinger KR, Singla A, Gerkowicz S, Dicke JM, Gray
DL, Odibo AO. Predicting the risk of pre-eclampsia between 11 and 13 weeks’ gestation by combining mater- nal characteristics and serum analytes, PAPP-A and free beta-hCG. Prenat Diagn 2010;30:1138–42. (Level II-3) [PubMed] [Full Text] A
103. Morris RK, Malin G, Robson SC, Kleijnen J, Zamora J, Khan KS. Fetal umbilical artery Doppler to predict compromise of fetal/neonatal wellbeing in a high- risk population: systematic review and bivariate meta- analysis. Ultrasound Obstet Gynecol 2011;37:135–42. (Meta-analysis) [PubMed] [Full Text] A
104. Silver RM, Varner MW, Reddy U, Goldenberg R, Pinar H, Conway D, et al. Work-up of stillbirth: a review of the evidence. Am J Obstet Gynecol 2007;196:433–44. (Level III) [PubMed] [Full Text] A 105. Kafatos AG, Vlachonikolis IG, Codrington CA. Nutrition
during pregnancy: the effects of an educational interven-tion program in Greece. Am J Clin Nutr 1989;50:970–9. (Level II-1) [PubMed] [Full Text] A 106. Khoury J, H enriksen T, Christophersen B, Tonstad S.
Effect of a cholesterol-lowering diet on maternal, cord,
1132 Practice Bulletin Fetal Growth Restriction OBSTETRICS & GYNECOLOGY
perinatal outcome in intrauterine growth restriction. Am J Obstet Gynecol 1999;180:750–6. (Level II-3) [PubMed] A
131. A randomised trial of timed delivery for the compro-mised preterm fetus: short term outcomes and Bayesian interpretation. GRIT Study Group. BJOG 2003;110: 27–32. (Level I) [PubMed] [Full Text] A 132. Thornton JG, H ornbuckle J, Vail A, Spiegelhalter DJ,
Levene M. Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multi-centred randomised controlled trial. GRIT study group. Lancet 2004;364:513–20. (Level I) [PubMed] [Full Text] A 133. Walker DM, Marlow N, Upstone L, Gross H, Hornbuckle
J, Vail A, et al. The Growth Restriction Intervention Trial: long-term outcomes in a randomized trial of tim-ing of delivery in fetal growth restriction. Am J Obstet Gynecol 2011;204:34.e1–34.e9. (Level I) [PubMed] [Full Text] A 134. Boers KE, Vijgen SM, Bijlenga D, van der Post JA,
Bekedam DJ, Kwee A, et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). DIGITAT Study Group. BMJ 2010;341:c7087. (Level I) [PubMed] [Full Text] A 135. Spong CY, Mercer BM, D’Alton M, Kilpatrick S,
Blackwell S, Saade G. Timing of indicated late-preterm and early-term birth. Obstet Gynecol 2011;118:323–33. (Level III) [PubMed] [Obstetrics & Gynecology ] A 136. Antenatal corticosteroids revisited: repeat courses. NIH
Consens Statement 2000;17:1–18. (Level III) [PubMed] A 137. Roberts D, Dalziel SR. Antenatal corticosteroids for
accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004454. DOI: 10.1002/146 51858.CD004454.pub2. (Meta-analysis) [PubMed] [Full Text] A 138. Effect of corticosteroids for fetal maturation on perina-tal outcomes. NIH Consens Statement 1994;12:1–24. (Level III) [PubMed] A 139. Crowther CA, Verkuyl DA, Neilson JP, Bannerman C,
Ashurst H M. The effects of hospitalization for rest on fetal growth, neonatal morbidity and length of gestation in twin pregnancy. Br J Obstet Gynaecol 1990;97:872–7. (Level I) [PubMed] A 140. Marret S, Marpeau L, Zupan-Simunek V, Eurin D,
Leveque C, Hellot MF, et al. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*. PREMAG Trial Group. BJOG 2007;114:310–8. (Level I) [PubMed] [Full Text] A 141. Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY,
Mercer BM, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. Eunice Kennedy Shriver NICH D Maternal–Fetal Med- icine Units Network. N Engl J Med 2008;359:895–905. (Level I) [PubMed] [Full Text] A
117. Gulmezolu M, de Onis M, Villar J. Effectiveness of inter-ventions to prevent or treat impaired fetal growth. Obstet Gynecol Surv 1997;52:139–49. (Level III) [PubMed] A 118. Leitich, Egarter C, Husslein P, Kaider A, Schemper M.
A meta-analysis of low dose aspirin for the prevention of intrauterine growth retardation. Br J Obstet Gynaecol 1997;104:450–9. (Meta-analysis) [PubMed] A 119. Bahado-Singh RO, Lynch L, Deren O, Morroti R, Copel
JA, Mahoney MJ, et al. First-trimester growth restriction and fetal aneuploidy: the effect of type of aneuploidy and gestational age. Am J Obstet Gynecol 1997;176:976–80. (Level II-3) [PubMed] [Full Text] A 120. Sassoon DA, Castro LC, Davis JL, Hobel CJ. Perinatal
outcome in triplet versus twin gestations. Obstet Gynecol 1990;75:817–20. (Level II-2) [PubMed] [Obstetrics & Gynecology ] A 121. Alexandr JM, Hammond KR, Steinkampf MP. Multifetal
reduction of high-order multiple pregnancy: comparison of obstetrical outcome with nonreduced twin gestations. Fertil Steril 1995;64:1201–3. (Level III) [PubMed] A 122. Silver R, H elfand BT, Russell TL, Ragin A, Sholl
JS, MacGregor SN. Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: a case-control study. Fertil Steril 1997;67:30–3. (Level II-2) [PubMed] [Full Text] A 123. Multiplegestation: complicated twin, triplet, and high-order multifetal pregnancy. ACOG Practice Bulletin No. 56. American College of Obstetricians and Gynecologists. Obstet Gynecol 2004;104:869–83. (Level III) [PubMed] [Obstetrics & Gynecology ] A 124. Machin A. Velamentous cord insertion in monochori-onic twin gestation. An added risk factor. J Reprod Med 1997;42:785–9. (Level III) [PubMed] A 125. Divon MY, Chamberlain PF, Sipos L, Manning FA, Platt
LD. Identification of the small for gestational age fetus with the use of gestational age-independent indices of fetal growth. Am J Obstet Gynecol 1986;155:1197–201. (Level II-3) [PubMed] A 126. Mongelli M, Ek S, Tambyrajia R. Screening for fetal
growth restriction: a mathematical model of the effect of time interval and ultrasound error. Obstet Gynecol 1998;92:908–12. (Level II-3) [PubMed] [Obstetrics & Gynecology ] A 127. Arabin B, Bergmann PL, Saling E. Simultaneous assess-ment of blood flow velocity waveforms in uteroplacental vessels, the umbilical artery, the fetal aorta and the fetal common carotid artery. Fetal Ther 1987;2:17–26. (Level III) [PubMed] A 128. Veille JC, Kanaan C. Duplex Doppler ultrasonographic
evaluation of the fetal renal artery in normal and abnor-mal fetuses. Am J Obstet Gynecol 1989;161:1502–7. (Level III) [PubMed] A 129. Gramellini D, Folli MC, Raboni S, Vadora E, Merialdi A.
Cerebral-umbilical Doppler ratio as a predictor of adverse perinatal outcome. Obstet Gynecol 1992;79:416–20. (Level III) [PubMed] [Obstetrics & Gynecology ] A 130. Bahado-Singh RO, Kovanci E, Jeffres A, Oz U, Deren O,
Copel J, et al. The Doppler cerebroplacental ratio and
VOL. 121, NO. 5, MAY 2013 Practice Bulletin Fetal Growth Restriction
1133
142. Magnesium sulfate before anticipated preterm birth for
neuroprotection. Committee Opinion No. 455. American College of Obstetricians and Gynecologists. Obstet Gyne-col 2010;115:669–71. (Level III) [PubMed] [Obstetrics & Gynecology ] A