- Email: [email protected]
Fetal Growth Restriction at Term: Myth or Reality?
Fetal Growth Restriction at Term: Myth or Reality? VICTORIA K. MINIOR AND MICHAEL Y. DIVON, MD Objective: To evaluate the morbidity and mortality associated with the small for gestational age (SGA) fetus born at term to an otherwise uncomplicated pregnancy. Methods: Small for gestational age, singleton newborns (birth weight below the tenth percentile for gestational age) born at 37– 42 weeks’ gestation were identified by medical record discharge coding. We excluded gestations complicated by structural or chromosomal abnormalities, maternal diabetes mellitus, preeclampsia, chronic hypertension, asthma, or renal, endocrine, or autoimmune disease. Three low-risk, appropriate for gestational age (AGA) fetuses, matched for gestational age at delivery, were selected randomly for each SGA fetus and served as controls. Maternal and neonatal data were abstracted via medical record review. Statistical analysis included x2 Fisher exact test, and analysis of variance. Results: There were 67 newborns in the study group and 201 in the control group. There were no fetal or neonatal deaths in any of these cases. The maternal age at delivery, prepregnancy weight, race, smoking status, weight gain during pregnancy, and neonatal gender did not statistically differ between the two groups. Compared with AGA infants, a larger proportion of SGA newborns had low 1-minute Apgar scores and SGA newborns were more likely to be admitted to the neonatal intensive care unit, and have respiratory distress, hypoglycemia, thrombocytopenia, and hyperbilirubinemia. They were also significantly more likely to be delivered by cesarean. Conclusion: The SGA newborn from an uncomplicated pregnancy delivered at term has increased neonatal morbidity compared with its AGA counterpart. These results dispute the notion that term growth restriction is a benign condition. (Obstet Gynecol 1998;92:57– 60. © 1998 by The American College of Obstetricians and Gynecologists.)
Small for gestational age (SGA) fetuses exhibit increased perinatal morbidity and mortality compared with their appropriate for gestational age (AGA) counterparts. These small fetuses have been reported to have From the Departments of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, New York, and the Lenox Hill Hospital, New York, New York.
VOL. 92, NO. 1, JULY 1998
an increased mortality rate as well as an increased incidence of fetal asphyxia, abnormal fetal heart rate patterns, meconium aspiration, and low Apgar scores.1 Hypoglycemia, thrombocytopenia, neonatal sepsis, polycythemia, hypothermia, pulmonary hemorrhage, hyperbilirubinemia, hypocalcemia, chromosomal and congenital malformations, and a prolonged neonatal intensive care unit (NICU) stay are more common in the SGA neonate, compared with the AGA infant.1,2 For some SGA infants, the postnatal period may be characterized by poor growth and development.3 Additionally, learning difficulties, speech defects, and mild neurologic and behavioral deficits have been shown to be significantly increased in children born SGA.4 –7 Small for dates infants also may be at increased risk for developing diabetes, high blood pressure, and cardiovascular disease as adults.8 Adverse perinatal outcome often is associated with complications of pregnancy such as maternal preeclampsia, chronic maternal disease, fetal congenital infections, and congenital and chromosomal fetal anomalies; these in turn are associated with fetal growth restriction (FGR).9 However, a paucity of data exists regarding the outcome of SGA fetuses that are the products of uncomplicated pregnancies. It has been suggested that SGA newborns of 37 weeks’ gestation or more are at no higher risk for adverse perinatal outcome.10,11 Because the definition of SGA is based on a birth-weight cutoff at an arbitrary centile of the Gaussian distribution (usually less than the tenth percentile), not all infants falling into this bottom tenth percentile will be abnormally small. Instead, they may be normally grown infants who have reached their full genetic potential at the lower end of the statistical range. Chard et al10 proposed that fullterm SGA infants who are products of uncomplicated pregnancies must be those infants who are normally grown and at no risk of adverse perinatal outcome. However, they provided no data of their own to support this hypothesis, supporting it rather with the work
0029-7844/98/$19.00 PII S0029-7844(98)00118-5
57
of several other investigators. Jones and Robertson12 studied a group of term SGA infants without control comparisons. They concluded that neonatal morbidity in the SGA infant is uncommon and transient and that the majority of SGA neonates are healthy and do not require NICU care.12 Although 19% of their SGA population had some morbidity, they “see no point” in screening term SGA infants for complications unless their birth weight is below the 2.3 centile (ie, 2 standard deviations below the mean).12 Robertson et al13 studied 20,680 neonates from uncomplicated pregnancies at various gestational ages and observed low rates of morbidity in term infants weighing less than 2500 g. However, they did not report a comparison between term SGA and AGA newborns. Kramer et al1 reported that the smallest (bottom 4.3 centile), term, growthrestricted infants have only a 1% increase in mortality over the normally grown population. However, the authors evaluated all growth-restricted fetuses without separating the complicated from the uncomplicated pregnancies. Ott11 compared term SGA and AGA neonates from his high-risk obstetric clinic. He found that there were no differences in mortality, morbidity, or length of stay in the NICU between the two groups.11 However, he did not exclude complicated pregnancies, which made up at least 39% of his population. The purpose of this study was to assess the risk for adverse perinatal outcome in the term SGA fetus that is a product of an otherwise uncomplicated pregnancy.
Materials and Methods One hundred eighty singleton, SGA infants (birth weight below the 10th percentile for gestational age)14 were identified via retrospective review of computerized medical record discharge coding. These infants were born at the Jack D. Weiler Hospital of the Albert Einstein College of Medicine between November 1988 and June 1995 and had accurate gestational age dating by last menstrual period and early ultrasound examination. One hundred and eight of these infants were born at term (gestational age 37– 42 weeks). To further limit the subset to include only uncomplicated pregnancies, we excluded all cases that demonstrated known high-risk conditions such as preeclampsia, chronic hypertension, diabetes mellitus, hemoglobinopathies, asthma, renal disease, autoimmune disease, and endocrine dysfunction (n 5 34). Seven infants with chromosomal or severe anatomic anomalies also were excluded. The remaining study group consisted of 67 neonates. Three gestational-age matched, AGA control infants were selected at random for each study infant, thus creating a control group of 201 singletons whose birth weight was greater than the tenth percentile for
58 Minior and Divon
Growth Restriction at Term
Table 1. Maternal Factors in Uncomplicated Term Small for Gestational Age and Appropriate for Gestational Age Infants
Maternal age (y)* Prepregnancy weight (kg)* Pregnancy weight gain (kg)* Maternal height (cm)* Race White (%) Black (%) Hispanic (%) Other (%) Smokers (%) Male infants (%)
SGA (n 5 67)
AGA (n 5 201)
P
28.8 6 6.8 61.3 6 12.8 13.9 6 6.7 159.2 6 5.6
29.3 6 5.4 64.5 6 14.7 14.4 6 5.9 162.8 6 8.5
NS NS NS .01
16 (24) 28 (42) 20 (30) 3 (4) 15 (22) 32 (48)
78 (39) 56 (28) 52 (26) 15 (7) 25 (12) 114 (57)
NS
NS NS
SGA 5 small for gestational age; AGA 5 appropriate for gestational age. * Mean 6 standard deviation.
gestational age. Control infants were born between January and October of 1995. The control infants resulted from low-risk, uncomplicated pregnancies and had normal chromosomes and anatomy. Medical records of mothers and infants were reviewed for maternal complications of pregnancy, smoking status, prepregnancy weight and height, pregnancy weight gain, gestational age at delivery, birth weight, and Apgar scores. In addition, data were abstracted regarding neonatal complications such as intubation in the delivery room, admission to the NICU, neonatal respiratory distress, sepsis, hypoglycemia, intraventricular hemorrhage, apnea, thrombocytopenia, and hyperbilirubinemia. Results were analyzed using Statview 4.5 (Abacus Concepts, Berkeley, CA) by analysis of variance and x2. Fisher exact test was used in comparisons involving small numbers. P , .05 was considered significant.
Results The study group consisted of 67 SGA neonates with a mean birth weight of 2337 6 278 g (6 standard deviation) and a mean gestational age at delivery of 39.3 6 1.4 weeks. The control group had a mean birth weight of 3397 6 457 g (P , .001) and a mean gestational age that was virtually identical to that of the study group. The maternal age at delivery, prepregnancy weight, race, smoking status, weight gain during pregnancy, and neonatal gender did not differ significantly between the two groups. However, maternal height was significantly greater in the control group (Table 1). Perinatal morbidity in study and control infants is shown in Table 2. The SGA newborns were significantly more likely to be delivered by cesarean, and a larger proportion had low 1-minute Apgar scores. Small for
Obstetrics & Gynecology
gestational age infants were more likely to be admitted to the NICU than AGA infants and had longer NICU stays. Additionally, there was a higher incidence of neonatal respiratory distress, hypoglycemia, thrombocytopenia, and hyperbilirubinemia in SGA infants. Small for gestational age infants were also more likely to be intubated during the course of their neonatal care, although this comparison did not reach statistical significance (P 5 .06) using Fisher exact test. When overall morbidity was examined, 19 of 67 (28%) SGA infants had one or more neonatal complication versus 11 of 201 (5%) AGA infants (P , .001). Excluding hyperbilirubinemia from the previous analysis, 15 of 67 (22%) SGA infants had a complicated neonatal course versus only five of 201 (2%) AGA infants (P , .001). There were no neonatal deaths in either the study or control group. To examine whether the smallest neonates in the study group had the highest morbidity, birth weight percentiles were derived for each infant. Infants were divided into three birth weight categories: 1) greater than or equal to the tenth percentile for gestational age (AGA infants), 2) between the tenth and fifth percentile, and 3) less than the fifth percentile. Table 3 demonstrates that the smallest infants were most likely to be admitted to the NICU, were most likely to be intubated, and had significantly longer NICU stays. When overall morbidity was examined, “sick” infants (with one or more neonatal complication) were most common in the less than fifth percentile group and least common in the AGA group. Interestingly, the smallest infants also had the most advanced gestational age. However, the clinical implication of this observation may be limited by its weak statistical significance. Table 2. Perinatal Morbidity in Uncomplicated Term Small for Gestational Age and Appropriate for Gestational Age Infants
Cesarean delivery Admission to the NICU Hypoglycemia Respiratory distress Thrombocytopenia Hyperbilirubinemia Intubated Sepsis Intraventricular hemorrhage Apnea Apgar score at 1 min # 7 Apgar score at 5 min # 7 Length of NICU stay (d)*
SGA (n 5 67) n (%)
AGA (n 5 201) n (%)
P
21 (31) 16 (24) 8 (12) 6 (9) 3 (4) 7 (10) 2 (3) 1 (1) 1 (1) 1 (1) 12 (18) 0 2.2 6 4.7
32 (16) 5 (2) 2 (1) 3 (1) 0 6 (3) 0 1 (1) 0 0 11 (5) 1 (1) 0.1 6 0.7
.02 , .001 , .001 .009 .02 .02 NS NS NS NS .002 NS , .001
SGA 5 small for gestational age; AGA 5 appropriate for gestational age; NICU 5 neonatal intensive care unit. * Results reported as mean 6 standard deviation.
VOL. 92, NO. 1, JULY 1998
Table 3. Neonatal Morbidity in Relation to Birth Weight Percentile ,5th $10th ,10th and $5th percentile percentile percentile (n 5 40) (n 5 27) (n 5 201) Sick infants 6 (3%) Intubated 0 Admitted to NICU 6 (3%) NICU stay (d)* 0.1 6 0.8 Gestational age (wk)* 39.2 6 1.3
2 (7%) 0 2 (7%) 0.8 6 3.1 39.3 6 1.6
P
10 (25%) , .001 1 (3%) .03 10 (25%) , .001 2.2 6 4.8 , .001 39.7 6 1.3 .04
NICU 5 neonatal intensive care unit. * Mean 6 standard deviation.
Discussion The results of this study indicate that perinatal morbidity is increased in the SGA fetus born at term following an otherwise uncomplicated pregnancy. Our results cannot be attributed to an excess of smoking mothers or male infants in the population or to racial differences between groups. Compared with AGA infants, SGA infants were more likely to have low Apgar scores and require NICU admission. Hypoglycemia, respiratory distress, thrombocytopenia, hyperbilirubinemia, and lengthy NICU stays were significantly more likely in the term SGA infant. In addition, mothers of SGA infants were more likely to undergo operative deliveries. That term SGA newborns were admitted to the NICU and had an extended NICU stay implies that this is a serious complication of pregnancy that should not be ignored as some authors have suggested.10 –12 Our findings are similar to those reported by other authors. Kramer et al1 observed that term SGA infants were significantly more likely to have low Apgar scores and hypoglycemia. Arora et al15 found that SGA infants born at term had higher rates of hypoglycemia and physiologic jaundice, compared with term AGA neonates. Our findings also confirm an investigation by Owen et al,16 who examined growth velocity of the fetal abdominal area in the third trimester and found that infants with low growth velocities were significantly more likely to be delivered by cesarean for fetal distress and were more likely to be admitted to the NICU. Hypoglycemia was the most common neonatal disorder diagnosed in our SGA population. This is consistent with decreased stores of liver glycogen in a nutritionally deprived infant. Thrombocytopenia in the growth-restricted infant is consistent with an increase in intraplacental coagulative processes seen in growthrestricted placentas.17 Hyperbilirubinemia may occur as a result of increased postnatal hemolysis in a polycythemic, growth-restricted infant who has been delivered from a relatively hypoxic environment into an oxygen replete extrauterine world. These findings sug-
Minior and Divon
Growth Restriction at Term
59
gest that pathologic processes result in growth restriction in uncomplicated SGA pregnancies delivered at term. There was a small but statistically significant difference in maternal height between the two groups. Mothers of SGA neonates were somewhat shorter than mothers of AGA neonates. This finding suggests that a proportion of the infants labeled SGA by our birth weight criteria were actually small babies born to small mothers. This study has several limitations. It is retrospective and involves a small number of infants. The control group was not matched for several variables, such as smoking status or race, that could affect birth weight. Although the two groups did not differ significantly in the number of smokers or the racial distribution, we cannot assume that these variables did not influence outcome. Additionally, we were unable to determine how prenatal detection of FGR might have influenced outcome. Failed inductions for FGR may have lead to an increase in the cesarean delivery rate in the SGA group. Jones and Robertson12 proposed that term SGA infants have no additional morbidity and mortality when compared with the normally grown population and should not be a source of perinatal concern. We disagree with their opinion. The present study demonstrates an excess of perinatal morbidity (28%) in the SGA population compared with 6% in normally grown fetuses. Jones and Robertson12 also proposed that morbidity in the SGA infant occurs only in those infants whose birth weight falls in the bottom 2.3 percentile. Indeed, we find that the smallest SGA neonates (those smaller than the fifth percentile) are more likely to have a complicated neonatal course compared with larger SGA infants and AGA infants. However, SGA infants whose birth weights are between the 5th and 10th percentile still have considerable morbidity compared with the AGA population; therefore, these infants cannot be ignored and still should be considered at increased risk for perinatal morbidity.
References 1. Kramer MS, Olivier M, McLean FH, Willis DM, Usher RH. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990;86:707–13. 2. Battaglia FC. Intrauterine growth retardation. Am J Obstet Gynecol 1970;106:1103–13. 3. Ounsted MK, Moar VA, Scott A. Children of deviant birth weight at the age of seven years: Health, handicap, size and developmental status. Early Hum Dev 1984;9:323– 40.
60 Minior and Divon
Growth Restriction at Term
4. McCarton CM, Wallace IF, Divon M, Vaughan HG. Cognitive and neurologic development of the premature, small for gestational age infant through age 6: Comparison by birth weight and gestational age. Pediatrics 1996;98:1167–78. 5. Low JA, Handley-Derry MH, Burke SO, Peters RD, Pater EA, Killen HL, et al. Association of intrauterine fetal growth retardation and learning deficits at age 9 to 11 years. Am J Obstet Gynecol 1992;167:1499 –1505. 6. Walther FJ, Ramaekers LH. Language development at the age of 3 years of infants malnourished in utero. Neuropediatrics 1982;13: 77– 81. 7. Hill RM, Verniaud WM, Deter RL, Tennyson LM, Rettig GM, Zion TE, et al. The effect of intrauterine malnutrition on the term infant. Acta Pediatr Scand 1984;73:482–7. 8. Barker DJ. Fetal growth and adult disease. Br J Obstet Gynaecol 1992;99:275– 82. 9. Ounsted M, Moar V, Scott WA. Perinatal morbidity and mortality in small for dates babies: The relative importance of some maternal factors. Early Hum Dev 1981;5:367–375. 10. Chard T, Yoong A, Macintosh M. The myth of fetal growth retardation at term. Br J Obstet Gynaecol 1993;100:1076 – 81. 11. Ott WJ. Small for gestational age fetus and neonatal outcome: Reevaluation of the relationship. Am J Perinatol 1995;12:396 – 400. 12. Jones RA, Robertson NR. Small for dates babies: Are they really a problem? Arch Dis Child 1986;61:877– 80. 13. Robertson PA, Sniderman SH, Laros RK, Cowan R, Heilbron D, Goldenberg RL, et al. Neonatal morbidity according to gestational age and birth weight from five tertiary centers in the United States, 1983 through 1986. Am J Obstet Gynecol 1992;166:1629 – 45. 14. Brenner WE, Edelman DA, Hendricks CH. A standard of fetal growth for the United States of America. Am J Obstet Gynecol 1976;126:555– 64. 15. Arora NK, Paul VK, Singh M. Morbidity and mortality in term infants with intrauterine growth retardation. J Trop Pediatr 1987; 33:186 –9. 16. Owen P, Harrold AJ, Farrell T. Fetal size and growth velocity in the prediction of intrapartum cesarean section for fetal distress. Br J Obstet Gynaecol 1997;104:445–9. 17. Salafia CM, Pezzullo JC, Minior VK, Divon MY. Placental pathology of absent and reversed end-diastolic flow in growth restricted fetuses. Obstet Gynecol 1997;90:830 – 6.
Address reprint requests to:
Michael Y. Divon, MD Jack D. Weiler Hospital of the Albert Einstein College of Medicine Room 703 1825 Eastchester Road Bronx, NY 10461-2373 E-mail: [email protected]
Received November 14, 1997. Received in revised form February 23, 1998. Accepted March 12, 1998. Copyright © 1998 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology
Small for gestational age (SGA) fetuses exhibit increased perinatal morbidity and mortality compared with their appropriate for gestational age (AGA) counterparts. These small fetuses have been reported to have From the Departments of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, New York, and the Lenox Hill Hospital, New York, New York.
VOL. 92, NO. 1, JULY 1998
an increased mortality rate as well as an increased incidence of fetal asphyxia, abnormal fetal heart rate patterns, meconium aspiration, and low Apgar scores.1 Hypoglycemia, thrombocytopenia, neonatal sepsis, polycythemia, hypothermia, pulmonary hemorrhage, hyperbilirubinemia, hypocalcemia, chromosomal and congenital malformations, and a prolonged neonatal intensive care unit (NICU) stay are more common in the SGA neonate, compared with the AGA infant.1,2 For some SGA infants, the postnatal period may be characterized by poor growth and development.3 Additionally, learning difficulties, speech defects, and mild neurologic and behavioral deficits have been shown to be significantly increased in children born SGA.4 –7 Small for dates infants also may be at increased risk for developing diabetes, high blood pressure, and cardiovascular disease as adults.8 Adverse perinatal outcome often is associated with complications of pregnancy such as maternal preeclampsia, chronic maternal disease, fetal congenital infections, and congenital and chromosomal fetal anomalies; these in turn are associated with fetal growth restriction (FGR).9 However, a paucity of data exists regarding the outcome of SGA fetuses that are the products of uncomplicated pregnancies. It has been suggested that SGA newborns of 37 weeks’ gestation or more are at no higher risk for adverse perinatal outcome.10,11 Because the definition of SGA is based on a birth-weight cutoff at an arbitrary centile of the Gaussian distribution (usually less than the tenth percentile), not all infants falling into this bottom tenth percentile will be abnormally small. Instead, they may be normally grown infants who have reached their full genetic potential at the lower end of the statistical range. Chard et al10 proposed that fullterm SGA infants who are products of uncomplicated pregnancies must be those infants who are normally grown and at no risk of adverse perinatal outcome. However, they provided no data of their own to support this hypothesis, supporting it rather with the work
0029-7844/98/$19.00 PII S0029-7844(98)00118-5
57
of several other investigators. Jones and Robertson12 studied a group of term SGA infants without control comparisons. They concluded that neonatal morbidity in the SGA infant is uncommon and transient and that the majority of SGA neonates are healthy and do not require NICU care.12 Although 19% of their SGA population had some morbidity, they “see no point” in screening term SGA infants for complications unless their birth weight is below the 2.3 centile (ie, 2 standard deviations below the mean).12 Robertson et al13 studied 20,680 neonates from uncomplicated pregnancies at various gestational ages and observed low rates of morbidity in term infants weighing less than 2500 g. However, they did not report a comparison between term SGA and AGA newborns. Kramer et al1 reported that the smallest (bottom 4.3 centile), term, growthrestricted infants have only a 1% increase in mortality over the normally grown population. However, the authors evaluated all growth-restricted fetuses without separating the complicated from the uncomplicated pregnancies. Ott11 compared term SGA and AGA neonates from his high-risk obstetric clinic. He found that there were no differences in mortality, morbidity, or length of stay in the NICU between the two groups.11 However, he did not exclude complicated pregnancies, which made up at least 39% of his population. The purpose of this study was to assess the risk for adverse perinatal outcome in the term SGA fetus that is a product of an otherwise uncomplicated pregnancy.
Materials and Methods One hundred eighty singleton, SGA infants (birth weight below the 10th percentile for gestational age)14 were identified via retrospective review of computerized medical record discharge coding. These infants were born at the Jack D. Weiler Hospital of the Albert Einstein College of Medicine between November 1988 and June 1995 and had accurate gestational age dating by last menstrual period and early ultrasound examination. One hundred and eight of these infants were born at term (gestational age 37– 42 weeks). To further limit the subset to include only uncomplicated pregnancies, we excluded all cases that demonstrated known high-risk conditions such as preeclampsia, chronic hypertension, diabetes mellitus, hemoglobinopathies, asthma, renal disease, autoimmune disease, and endocrine dysfunction (n 5 34). Seven infants with chromosomal or severe anatomic anomalies also were excluded. The remaining study group consisted of 67 neonates. Three gestational-age matched, AGA control infants were selected at random for each study infant, thus creating a control group of 201 singletons whose birth weight was greater than the tenth percentile for
58 Minior and Divon
Growth Restriction at Term
Table 1. Maternal Factors in Uncomplicated Term Small for Gestational Age and Appropriate for Gestational Age Infants
Maternal age (y)* Prepregnancy weight (kg)* Pregnancy weight gain (kg)* Maternal height (cm)* Race White (%) Black (%) Hispanic (%) Other (%) Smokers (%) Male infants (%)
SGA (n 5 67)
AGA (n 5 201)
P
28.8 6 6.8 61.3 6 12.8 13.9 6 6.7 159.2 6 5.6
29.3 6 5.4 64.5 6 14.7 14.4 6 5.9 162.8 6 8.5
NS NS NS .01
16 (24) 28 (42) 20 (30) 3 (4) 15 (22) 32 (48)
78 (39) 56 (28) 52 (26) 15 (7) 25 (12) 114 (57)
NS
NS NS
SGA 5 small for gestational age; AGA 5 appropriate for gestational age. * Mean 6 standard deviation.
gestational age. Control infants were born between January and October of 1995. The control infants resulted from low-risk, uncomplicated pregnancies and had normal chromosomes and anatomy. Medical records of mothers and infants were reviewed for maternal complications of pregnancy, smoking status, prepregnancy weight and height, pregnancy weight gain, gestational age at delivery, birth weight, and Apgar scores. In addition, data were abstracted regarding neonatal complications such as intubation in the delivery room, admission to the NICU, neonatal respiratory distress, sepsis, hypoglycemia, intraventricular hemorrhage, apnea, thrombocytopenia, and hyperbilirubinemia. Results were analyzed using Statview 4.5 (Abacus Concepts, Berkeley, CA) by analysis of variance and x2. Fisher exact test was used in comparisons involving small numbers. P , .05 was considered significant.
Results The study group consisted of 67 SGA neonates with a mean birth weight of 2337 6 278 g (6 standard deviation) and a mean gestational age at delivery of 39.3 6 1.4 weeks. The control group had a mean birth weight of 3397 6 457 g (P , .001) and a mean gestational age that was virtually identical to that of the study group. The maternal age at delivery, prepregnancy weight, race, smoking status, weight gain during pregnancy, and neonatal gender did not differ significantly between the two groups. However, maternal height was significantly greater in the control group (Table 1). Perinatal morbidity in study and control infants is shown in Table 2. The SGA newborns were significantly more likely to be delivered by cesarean, and a larger proportion had low 1-minute Apgar scores. Small for
Obstetrics & Gynecology
gestational age infants were more likely to be admitted to the NICU than AGA infants and had longer NICU stays. Additionally, there was a higher incidence of neonatal respiratory distress, hypoglycemia, thrombocytopenia, and hyperbilirubinemia in SGA infants. Small for gestational age infants were also more likely to be intubated during the course of their neonatal care, although this comparison did not reach statistical significance (P 5 .06) using Fisher exact test. When overall morbidity was examined, 19 of 67 (28%) SGA infants had one or more neonatal complication versus 11 of 201 (5%) AGA infants (P , .001). Excluding hyperbilirubinemia from the previous analysis, 15 of 67 (22%) SGA infants had a complicated neonatal course versus only five of 201 (2%) AGA infants (P , .001). There were no neonatal deaths in either the study or control group. To examine whether the smallest neonates in the study group had the highest morbidity, birth weight percentiles were derived for each infant. Infants were divided into three birth weight categories: 1) greater than or equal to the tenth percentile for gestational age (AGA infants), 2) between the tenth and fifth percentile, and 3) less than the fifth percentile. Table 3 demonstrates that the smallest infants were most likely to be admitted to the NICU, were most likely to be intubated, and had significantly longer NICU stays. When overall morbidity was examined, “sick” infants (with one or more neonatal complication) were most common in the less than fifth percentile group and least common in the AGA group. Interestingly, the smallest infants also had the most advanced gestational age. However, the clinical implication of this observation may be limited by its weak statistical significance. Table 2. Perinatal Morbidity in Uncomplicated Term Small for Gestational Age and Appropriate for Gestational Age Infants
Cesarean delivery Admission to the NICU Hypoglycemia Respiratory distress Thrombocytopenia Hyperbilirubinemia Intubated Sepsis Intraventricular hemorrhage Apnea Apgar score at 1 min # 7 Apgar score at 5 min # 7 Length of NICU stay (d)*
SGA (n 5 67) n (%)
AGA (n 5 201) n (%)
P
21 (31) 16 (24) 8 (12) 6 (9) 3 (4) 7 (10) 2 (3) 1 (1) 1 (1) 1 (1) 12 (18) 0 2.2 6 4.7
32 (16) 5 (2) 2 (1) 3 (1) 0 6 (3) 0 1 (1) 0 0 11 (5) 1 (1) 0.1 6 0.7
.02 , .001 , .001 .009 .02 .02 NS NS NS NS .002 NS , .001
SGA 5 small for gestational age; AGA 5 appropriate for gestational age; NICU 5 neonatal intensive care unit. * Results reported as mean 6 standard deviation.
VOL. 92, NO. 1, JULY 1998
Table 3. Neonatal Morbidity in Relation to Birth Weight Percentile ,5th $10th ,10th and $5th percentile percentile percentile (n 5 40) (n 5 27) (n 5 201) Sick infants 6 (3%) Intubated 0 Admitted to NICU 6 (3%) NICU stay (d)* 0.1 6 0.8 Gestational age (wk)* 39.2 6 1.3
2 (7%) 0 2 (7%) 0.8 6 3.1 39.3 6 1.6
P
10 (25%) , .001 1 (3%) .03 10 (25%) , .001 2.2 6 4.8 , .001 39.7 6 1.3 .04
NICU 5 neonatal intensive care unit. * Mean 6 standard deviation.
Discussion The results of this study indicate that perinatal morbidity is increased in the SGA fetus born at term following an otherwise uncomplicated pregnancy. Our results cannot be attributed to an excess of smoking mothers or male infants in the population or to racial differences between groups. Compared with AGA infants, SGA infants were more likely to have low Apgar scores and require NICU admission. Hypoglycemia, respiratory distress, thrombocytopenia, hyperbilirubinemia, and lengthy NICU stays were significantly more likely in the term SGA infant. In addition, mothers of SGA infants were more likely to undergo operative deliveries. That term SGA newborns were admitted to the NICU and had an extended NICU stay implies that this is a serious complication of pregnancy that should not be ignored as some authors have suggested.10 –12 Our findings are similar to those reported by other authors. Kramer et al1 observed that term SGA infants were significantly more likely to have low Apgar scores and hypoglycemia. Arora et al15 found that SGA infants born at term had higher rates of hypoglycemia and physiologic jaundice, compared with term AGA neonates. Our findings also confirm an investigation by Owen et al,16 who examined growth velocity of the fetal abdominal area in the third trimester and found that infants with low growth velocities were significantly more likely to be delivered by cesarean for fetal distress and were more likely to be admitted to the NICU. Hypoglycemia was the most common neonatal disorder diagnosed in our SGA population. This is consistent with decreased stores of liver glycogen in a nutritionally deprived infant. Thrombocytopenia in the growth-restricted infant is consistent with an increase in intraplacental coagulative processes seen in growthrestricted placentas.17 Hyperbilirubinemia may occur as a result of increased postnatal hemolysis in a polycythemic, growth-restricted infant who has been delivered from a relatively hypoxic environment into an oxygen replete extrauterine world. These findings sug-
Minior and Divon
Growth Restriction at Term
59
gest that pathologic processes result in growth restriction in uncomplicated SGA pregnancies delivered at term. There was a small but statistically significant difference in maternal height between the two groups. Mothers of SGA neonates were somewhat shorter than mothers of AGA neonates. This finding suggests that a proportion of the infants labeled SGA by our birth weight criteria were actually small babies born to small mothers. This study has several limitations. It is retrospective and involves a small number of infants. The control group was not matched for several variables, such as smoking status or race, that could affect birth weight. Although the two groups did not differ significantly in the number of smokers or the racial distribution, we cannot assume that these variables did not influence outcome. Additionally, we were unable to determine how prenatal detection of FGR might have influenced outcome. Failed inductions for FGR may have lead to an increase in the cesarean delivery rate in the SGA group. Jones and Robertson12 proposed that term SGA infants have no additional morbidity and mortality when compared with the normally grown population and should not be a source of perinatal concern. We disagree with their opinion. The present study demonstrates an excess of perinatal morbidity (28%) in the SGA population compared with 6% in normally grown fetuses. Jones and Robertson12 also proposed that morbidity in the SGA infant occurs only in those infants whose birth weight falls in the bottom 2.3 percentile. Indeed, we find that the smallest SGA neonates (those smaller than the fifth percentile) are more likely to have a complicated neonatal course compared with larger SGA infants and AGA infants. However, SGA infants whose birth weights are between the 5th and 10th percentile still have considerable morbidity compared with the AGA population; therefore, these infants cannot be ignored and still should be considered at increased risk for perinatal morbidity.
References 1. Kramer MS, Olivier M, McLean FH, Willis DM, Usher RH. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990;86:707–13. 2. Battaglia FC. Intrauterine growth retardation. Am J Obstet Gynecol 1970;106:1103–13. 3. Ounsted MK, Moar VA, Scott A. Children of deviant birth weight at the age of seven years: Health, handicap, size and developmental status. Early Hum Dev 1984;9:323– 40.
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Address reprint requests to:
Michael Y. Divon, MD Jack D. Weiler Hospital of the Albert Einstein College of Medicine Room 703 1825 Eastchester Road Bronx, NY 10461-2373 E-mail: [email protected]
Received November 14, 1997. Received in revised form February 23, 1998. Accepted March 12, 1998. Copyright © 1998 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology