- Email: [email protected]
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth
OBSTETRICS
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth Jordan C. Knight, DO,1 John O. Elliott, PhD,1 O. Laurie Amburgey, MD2 1
Department of Medical Education, Riverside Methodist Hospital, Columbus, OH
2
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Riverside Methodist Hospital, Columbus, OH
Abstract Objective: To evaluate the association between retroplacental leiomyoma identified on second trimester ultrasound and fetal growth. Methods: We performed a retrospective study comparing the presence or absence of one or more retroplacental leiomyomas on birth weight in a cohort of women with singleton pregnancies undergoing second trimester fetal anatomic ultrasound at our institution between 2007 and 2012. The incidence of small for gestational age (SGA) infants was recorded. Secondary analysis evaluated the effect of number and size of retroplacental leiomyomas. Results: Birth weight in women with at least one retroplacental leiomyoma was 177 grams less than in women without leiomyomas (95% CI 295 to 95, P ¼ 0.003). There was a non-significant trend towards a higher incidence of SGA in infants born to women with retroplacental leiomyoma compared with women without leiomyoma (OR 2.84; 95% CI 0.97 to 6.84, P ¼ 0.057). Women with a retroplacental leiomyoma > 4 cm in mean diameter were more likely to deliver an SGA infant than women without leiomyomas (OR 2.84, 95% CI 1.01 to 8.01; P ¼ 0.048). Multiple retroplacental leiomyomas did not have a greater effect on pregnancy outcomes than single leiomyomas. Conclusion: Infants born to women with one or more retroplacental leiomyomas had a lower mean birth weight than infants born to women without leiomyomas. In addition, retroplacental leiomyomas > 4 cm in mean diameter were associated with an increased risk of delivering an SGA infant.
Méthodologie : Nous avons réalisé une étude rétrospective portant sur une cohorte de femmes enceintes d’un seul fœtus ayant subi une échographie morphologique au deuxième trimestre dans notre établissement entre 2007 et 2012. Nous avons comparé le poids à la naissance selon qu’aucun, un ou plusieurs léiomyomes rétroplacentaires avaient été détectés et avons noté la fréquence de bébés petits pour l’âge gestationnel (PAG). Notre analyse secondaire portait sur l’incidence du nombre et de la taille des léiomyomes. Résultats : Le poids à la naissance des bébés de femmes présentant au moins un léiomyome rétroplacentaire était inférieur de 177 grammes à celui des bébés de femmes sans léiomyome (intervalle de confiance [IC] à 95 % : 295 à 95; P ¼ 0,003). Nous avons relevé une tendance non significative indiquant une fréquence supérieure de bébés PAG chez les mères présentant un ou plusieurs léiomyomes comparativement aux femmes n’en ayant pas (rapport de cotes [RC] : 2,84; IC à 95 % : 0,97 à 6,84; P ¼ 0,057). Les femmes présentant un léiomyome dont le diamètre moyen était > 4 cm étaient plus susceptibles d’accoucher d’un bébé PAG que celles ne présentant aucune masse (RC : 2,84; IC à 95 % : 1,01 à 8,01; P ¼ 0,048). La présence de plusieurs léiomyomes n’avait pas une incidence plus grande sur les issues de grossesse que celle d’une seule masse. Conclusion : Les nouveau-nés de femmes présentant un ou plusieurs léiomyomes rétroplacentaires avaient un poids à la naissance plus faible que ceux de mères qui n’en présentaient pas. Un diamètre moyen > 4 cm était associé à un risque accru de PAG. Published by Elsevier Inc. on behalf of the The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada
Résumé Objectif : Évaluer l’association entre la détection d’un léiomyome rétroplacentaire à l’échographie du deuxième trimestre et la croissance fœtale.
J Obstet Gynaecol Can 2016;38(12):1100e1104
INTRODUCTION Key Words: Fetal growth, retroplacental, leiomyoma, obstetric ultrasound Conflicting Interests: None declared. Presented as poster presentation at the 24th annual scientific meeting of the Society of Maternal Fetal Medicine, February 2e8, 2014, New Orleans, Louisiana. Received on July 11, 2016 Accepted on August 18, 2016 http://dx.doi.org/10.1016/j.jogc.2016.08.012
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eiomyomas arise from smooth muscle cells of the uterus and are the most common gynaecologic tumours. The prevalence of uterine leiomyomas in pregnancy ranges from 2% to 3.2%.1 Several studies have evaluated pregnancy complications associated with leiomyomas, including intrauterine growth restriction, fetal death, fetal malpresentation, placenta previa, delivery by Caesarean section, premature rupture of membranes, and preterm labour.1e6 Published data on obstetric outcomes in women
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth
with leiomyomas are conflicting. Stout et al. reported a low risk of obstetric complications for women with leiomyomas compared with women without leiomyomas; no difference in outcomes was noted in patients regardless of the size, number, or location of leiomyomas.1 However, other studies have suggested that women with leiomyomas were twice as likely to experience a complication during pregnancy.4e8 The specific outcome of fetal growth restriction in relation to the location of a leiomyoma has not been previously addressed. Leiomyomas may be found in different locations within the uterus during pregnancy. A retroplacental leiomyoma is defined as a smooth muscle neoplasm within the myometrium of the uterus and positioned beneath the site of placental implantation (Figure 1). There is a lack of published information about the possible effects of retroplacental leiomyomas on fetal growth. The hypothesis that a retroplacental leiomyoma may affect distribution of uterine blood flow with consequent fetal growth restriction is biologically plausible. The objective of this study was to evaluate the association between the presence of one or more retroplacental leiomyomas, identified on routine second trimester ultrasound assessment, and fetal growth. METHODS
We conducted a retrospective cohort study to assess the effect of having one or more retroplacental leiomyomas on fetal birth weight and the incidence of small for gestational age infants among women with singleton pregnancies undergoing routine second trimester fetal anatomic ultrasound at our institution between 2007 and 2012. Specialized obstetric and gynaecologic sonographers Figure 1. Ultrasound image showing a 6.2 cm right fundal retroplacental leiomyoma (RPL) adjacent to the placenta (P), identified on routine second trimester anatomic surveillance ultrasound
performed the ultrasound examinations. Final diagnoses and interpretations were determined by one of four attending maternal-fetal medicine physicians. In accordance with the American Institute of Ultrasound in Medicine guidelines for obstetric ultrasound examination,9 the presence, location, and size of all leiomyomas were recorded. In women with leiomyomas, data on leiomyoma number, size, location in the uterus, and location relative to the placenta were collected. Leiomyoma size was recorded using the largest diameter measured. We reviewed medical records to obtain maternal demographic data and medical comorbidities. Women who delivered outside our primary health care system were excluded from the analysis. Potential confounding factors for birth weight were identified as gestational diabetes, preexisting diabetes, chronic hypertension, and maternal tobacco use. Gestational diabetes was defined as a plasma glucose level of more than 7.8 mmol/L on a one-hour screening glucose challenge test followed by at least two abnormal values on a three-hour glucose tolerance test using the National Diabetes Data Group limit.10 Pre-gestational diabetes was defined as either type I or type II diabetes mellitus diagnosed before pregnancy. Chronic hypertension was defined as a systolic blood pressure of 140 mm Hg or a diastolic blood pressure of 90 mm Hg before 20 weeks of gestation or the use of antihypertensive medications before pregnancy. Delivery records were obtained from the Riverside Methodist Hospital medical record database. The primary outcomes were birth weight and the incidence of SGA, defined as a birth weight less than the 10th percentile for gestational age.11 Descriptive statistics were used to estimate the frequency of leiomyomas in the study population. The control group was randomly selected from patients without an ICD-9 diagnostic code for leiomyomas who were registered in the OhioHealth database for 2007e2012 and who underwent a routine second trimester anatomical ultrasound examination and delivered at an OhioHealth facility at a gestational age greater than 24 weeks (Figure 2). This control group was generated with a systemic random sampling method in order to obtain a sample size equivalent to the case group. Baseline demographic and medical characteristics of women with retroplacental leiomyomas were compared with women without leiomyomas using chi-square tests and student t tests. Multivariable linear and logistic regression analyses controlling for gestational age at
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Figure 2. Study flowchart Second trimester ultrasound paents 2007-2012
Cases ICD-9 leiomyoma (n = 453) Controls
> 1 Documented Retroplacental leiomyomata
No ICD-9 leiomyoma (n = 189)
(n = 172) Excluded (n = 31)
Excluded (n = 48)
Incomplete data: Prenatal history (n = 22) Delivery outcomes (n = 9)
Incomplete data: Prenatal history (n = 40) Delivery outcomes (n = 8) Cases
Controls
Complete records available
Complete records available
(n = 141)
(n = 141)
delivery, age, ethnicity, BMI, and medical comorbidities including chronic hypertension, gestational diabetes, and pre-existing diabetes were conducted to determine if retroplacental location was associated with altered birth weight and SGA. A separate linear regression analysis was conducted to identify the potential effect of number and size of leiomyoma. Statistical significance was based on traditional two-sided tests with the alpha error set at 5%. Statistical analyses were conducted using SPSS Statistics version 19.0 (IBM Corp., Armonk, NY).
Women with retroplacental leiomyomas were older, more likely to be African-American, and were more likely to have a higher BMI than those without leiomyomas. Gravidity, parity, and the incidence of other medical comorbidities (including gestational and pre-existing diabetes and chronic and gestational hypertension) were similar in both groups. Gestational age at delivery was significantly less in women with retroplacental leiomyomas than in women without leiomyomas (38.1 weeks vs. 39.2 weeks, P < 0.026), as was birth weight (3114.4 g vs. 3366.6 g, P < 0.001) (Table 1).
Ethics approval for the study was obtained from the Riverside Methodist Hospital/OhioHealth Institutional Review Board.
Birth weight, controlled for gestational age at delivery, was 177 g less in women with retroplacental leiomyoma than in women without leiomyomas (95% CI 295 g to 95 g, P ¼ 0.003).
RESULTS
A total of 14 156 women underwent routine second trimester ultrasound assessment at our institution between 2007 and 2012. The incidence of leiomyoma was 4.0% (n ¼ 453). Of women with documented leiomyomas, 38% had at least one retroplacental leiomyoma (n ¼ 172). Complete obstetric data, including prenatal history and delivery outcome, were available for 141 of these women (82%).
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After controlling for gestational age at delivery, there was a non-significant trend towards a higher incidence of SGA infants in women with retroplacental leiomyomas (n ¼ 22) compared with women without leiomyomas (n ¼ 9) (OR 2.58, 95% CI 0.97 to 6.84, P ¼ 0.057). Of the 141 women with retroplacental leiomyomas, 17 (12%) had a leiomyoma > 10 cm, 65 (46%) had a leiomyoma measuring between 4 cm and 10 cm, and 58 women (41%) had a leiomyoma measuring < 4 cm. The mean diameter of leiomyomas in
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth
Age in years
Retroplacental leiomyoma (n ¼ 141)
No leiomyoma (n ¼ 141)
34.2 (4.4)
31.5 (5.2)
Race/ethnicity
Pa <0.001 0.955
Caucasian
76
77
African American
47
31.2
Hispanic
4
6
Asian
5
4
Other
9
10
2.6 (1.6)
2.8 (1.6)
0.347
Parity
0.9 (1.2)
1.3 (1.2)
0.004
Gestational age at delivery in daysb
270.1 (15.7)
273.5 (8.2)
0.026
Birth weight in grams
3114.4 (628.0)
3366.6 (494.7)
0.001
BMI in kg/m2
6.38% 4.26% 1.42%
29.4 (8.0)
27.3 (7.1)
Mulple leiomyomas
Retroplacental leiomyoma < 4cm
Retroplacental leiomyoma > 4cm
DISCUSSION
Comorbidities (n)
0.023 1.000
Chorioamnionitis
1
0
Gestational hypertension
1
1
Chronic hypertension
9
9
Gestational diabetes
7
7
Pre-existing diabetes
3
3
Data are mean ± standard deviation unless otherwise specified. a P for comparison of women with retroplacental leiomyoma compared with women with no leiomyoma.
Based on ultrasound dating.
women with retroplacental leiomyomas was 5.05 cm (Table 2). Women with a retroplacental leiomyoma > 4 cm were more likely to have an SGA infant (n ¼ 16) than women without a leiomyoma (n ¼ 9) (OR 2.84, 95% CI 1.01 to 8.01, P ¼ 0.048) (Figure 3). The maximum number of retroplacental leiomyomas detected in an individual woman was three; the median number was one (130 women had 1, 9 women had 2, and 2 women had 3). There was no difference in birth weight between pregnant women with multiple retroplacental leiomyomas and pregnant women without leiomyoma (P ¼ 0.623). Table 2. Leiomyoma characteristics in pregnant women with retroplacental leiomyoma Characteristica Mean width in cm (SD)
5.01 (2.6)
Mean height in cm (SD)
5.05 (5.2)
Mean number of leiomyomas (SD)
1.1 (0.2)
a
11.35%
No leiomyoma
Gravidity
b
Figure 3. Proportion of SGA infants in pregnant women with no leiomyomas, multiple leiomyomas, and retroplacental leiomyomas
Percentage of SGA Infants
Table 1. Characteristics of pregnant women with retroplacental leiomyomas and pregnant women without leiomyomas
Leiomyoma size was determined by the largest diameter identified on ultrasound.
Infants born to women with one or more retroplacental leiomyomas have significantly lower birth weights than infants born to women without leiomyomas. Specifically, after controlling for gestational age at delivery and for other significant confounders including age, BMI, and maternal medical comorbities (chronic hypertension, gestational diabetes, and pre-existing diabetes), women with retroplacental leiomyomas were more likely to deliver an infant that was SGA than women without leiomyomas, although this trend did not reach statistical significance. However, retroplacental leiomyomas > 4 cm in maximal diameter were significantly associated with SGA. The mechanisms by which retroplacental leiomyomas increase the risk of low birth weight infants are unknown, but may include inflammation, alterations in the endometrium, and revascularization with redistribution of uterine blood flow. A previous study of leiomyoma size and number indicate that adverse obstetric outcomes including increased risk of low birth weight may be attributable to a global uterine effect.1 However, other studies have shown conflicting data regarding leiomyoma location and the relationship of leiomyomas to fetal growth.3,4 Our study is unique because it only compared women with retroplacental leiomyomas to women without leiomyomas. In this comparison, the increased rate of SGA infants suggests that the location of leiomyoma in relation to the placenta may have an impact on fetal growth, and that direct physical interaction between the placenta and the leiomyoma may increase the risk of low birth weight more than the global vascular effect of leiomyomas.1 However, this can only be speculated because we did not compare outcomes in women with retroplacental leiomyomas with
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outcomes in women with leiomyomas not located beneath the placental implantation site.
REFERENCES
We found that women with a retroplacental leiomyoma > 4 cm in maximum diameter were at risk for having SGA infants; these women may therefore benefit from having increased fetal growth surveillance during pregnancy.
1. Stout MJ, Odibo AO, Graseck AS, Macones GA, Crane JP, Cahill AG. Leiomyomas at routine second trimester ultrasound examination and adverse obstetric outcomes. Obstet Gynecol 2011;116:1056e63.
A strength of this study was that it included a large population of women with retroplacental leiomyomas with few confounding variables. The prevalence of leiomyomas in our study population was 4%, which is similar to previous reports.1 Limitations of the study include its retrospective nature, which inherently introduces bias. Although this study focused on the primary outcome of birth weight at delivery, future prospective studies should address other neonatal outcomes (e.g., admission to NICU, respiratory distress syndrome, length of NICU stay) to emphasize the clinical importance of identifying SGA infants.
3. Sheiner E, Bashiri A, Levy A, Hershkovitz R, Katz M, Mazor M. Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. J Repro Med 2004;49:182e6.
CONCLUSION
As women delay childbearing to their later reproductive years, the incidence of leiomyomas during pregnancy increases. The clinical effects of leiomyomas in pregnancy must be discussed in prenatal and antepartum counselling. We found that retroplacental leiomyomas are associated with decreased birth weight, and consequently increased fetal surveillance may be beneficial in women with this common uterine finding.
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2. Chen YH, Lin HC. Increased risk of preterm births among women with uterine leiomyoma: a nationwide population-based study. Hum Reprod 2009;24:3049e56.
4. Coronado GD, Marshall LM, Schwartz SM. Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population based study. Obstet Gynecol 2000;95:764e9. 5. Qidwai GI, Caughey AB, Jacoby AF. Obstetric outcomes in women with sonographically identified uterine leiomyomata. Obstet Gynecol 2006;107:376e82. 6. Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyomas in pregnancy. Am J Obstet Gynecol 1989;160:1212e6. 7. Davis JL, Ray-Mazumder S, Hobel CJ, Baley K, Sassoon D. Uterine leiomyomas in pregnancy: a prospective study. Obstet Gynecol 1990;75:41e4. 8. Katz VL, Dotters DJ, Droegemeuller W. Complications of uterine leiomyomas in pregnancy. Obstet Gynecol 1989;73:593e6. 9. American Institute of Ultrasound in Medicine. Practice guideline. Obstetric Ultrasound. Laurel (MD): American Institute of Ultrasound in Medicine; 2007. 10. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4e19. 11. Alexander GR, Himes JH, Kaufman RB, Mor O, Kogan M. A United States National reference for fetal growth. Obstet Gynecol 1996;87:163e8.
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth Jordan C. Knight, DO,1 John O. Elliott, PhD,1 O. Laurie Amburgey, MD2 1
Department of Medical Education, Riverside Methodist Hospital, Columbus, OH
2
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Riverside Methodist Hospital, Columbus, OH
Abstract Objective: To evaluate the association between retroplacental leiomyoma identified on second trimester ultrasound and fetal growth. Methods: We performed a retrospective study comparing the presence or absence of one or more retroplacental leiomyomas on birth weight in a cohort of women with singleton pregnancies undergoing second trimester fetal anatomic ultrasound at our institution between 2007 and 2012. The incidence of small for gestational age (SGA) infants was recorded. Secondary analysis evaluated the effect of number and size of retroplacental leiomyomas. Results: Birth weight in women with at least one retroplacental leiomyoma was 177 grams less than in women without leiomyomas (95% CI 295 to 95, P ¼ 0.003). There was a non-significant trend towards a higher incidence of SGA in infants born to women with retroplacental leiomyoma compared with women without leiomyoma (OR 2.84; 95% CI 0.97 to 6.84, P ¼ 0.057). Women with a retroplacental leiomyoma > 4 cm in mean diameter were more likely to deliver an SGA infant than women without leiomyomas (OR 2.84, 95% CI 1.01 to 8.01; P ¼ 0.048). Multiple retroplacental leiomyomas did not have a greater effect on pregnancy outcomes than single leiomyomas. Conclusion: Infants born to women with one or more retroplacental leiomyomas had a lower mean birth weight than infants born to women without leiomyomas. In addition, retroplacental leiomyomas > 4 cm in mean diameter were associated with an increased risk of delivering an SGA infant.
Méthodologie : Nous avons réalisé une étude rétrospective portant sur une cohorte de femmes enceintes d’un seul fœtus ayant subi une échographie morphologique au deuxième trimestre dans notre établissement entre 2007 et 2012. Nous avons comparé le poids à la naissance selon qu’aucun, un ou plusieurs léiomyomes rétroplacentaires avaient été détectés et avons noté la fréquence de bébés petits pour l’âge gestationnel (PAG). Notre analyse secondaire portait sur l’incidence du nombre et de la taille des léiomyomes. Résultats : Le poids à la naissance des bébés de femmes présentant au moins un léiomyome rétroplacentaire était inférieur de 177 grammes à celui des bébés de femmes sans léiomyome (intervalle de confiance [IC] à 95 % : 295 à 95; P ¼ 0,003). Nous avons relevé une tendance non significative indiquant une fréquence supérieure de bébés PAG chez les mères présentant un ou plusieurs léiomyomes comparativement aux femmes n’en ayant pas (rapport de cotes [RC] : 2,84; IC à 95 % : 0,97 à 6,84; P ¼ 0,057). Les femmes présentant un léiomyome dont le diamètre moyen était > 4 cm étaient plus susceptibles d’accoucher d’un bébé PAG que celles ne présentant aucune masse (RC : 2,84; IC à 95 % : 1,01 à 8,01; P ¼ 0,048). La présence de plusieurs léiomyomes n’avait pas une incidence plus grande sur les issues de grossesse que celle d’une seule masse. Conclusion : Les nouveau-nés de femmes présentant un ou plusieurs léiomyomes rétroplacentaires avaient un poids à la naissance plus faible que ceux de mères qui n’en présentaient pas. Un diamètre moyen > 4 cm était associé à un risque accru de PAG. Published by Elsevier Inc. on behalf of the The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada
Résumé Objectif : Évaluer l’association entre la détection d’un léiomyome rétroplacentaire à l’échographie du deuxième trimestre et la croissance fœtale.
J Obstet Gynaecol Can 2016;38(12):1100e1104
INTRODUCTION Key Words: Fetal growth, retroplacental, leiomyoma, obstetric ultrasound Conflicting Interests: None declared. Presented as poster presentation at the 24th annual scientific meeting of the Society of Maternal Fetal Medicine, February 2e8, 2014, New Orleans, Louisiana. Received on July 11, 2016 Accepted on August 18, 2016 http://dx.doi.org/10.1016/j.jogc.2016.08.012
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eiomyomas arise from smooth muscle cells of the uterus and are the most common gynaecologic tumours. The prevalence of uterine leiomyomas in pregnancy ranges from 2% to 3.2%.1 Several studies have evaluated pregnancy complications associated with leiomyomas, including intrauterine growth restriction, fetal death, fetal malpresentation, placenta previa, delivery by Caesarean section, premature rupture of membranes, and preterm labour.1e6 Published data on obstetric outcomes in women
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth
with leiomyomas are conflicting. Stout et al. reported a low risk of obstetric complications for women with leiomyomas compared with women without leiomyomas; no difference in outcomes was noted in patients regardless of the size, number, or location of leiomyomas.1 However, other studies have suggested that women with leiomyomas were twice as likely to experience a complication during pregnancy.4e8 The specific outcome of fetal growth restriction in relation to the location of a leiomyoma has not been previously addressed. Leiomyomas may be found in different locations within the uterus during pregnancy. A retroplacental leiomyoma is defined as a smooth muscle neoplasm within the myometrium of the uterus and positioned beneath the site of placental implantation (Figure 1). There is a lack of published information about the possible effects of retroplacental leiomyomas on fetal growth. The hypothesis that a retroplacental leiomyoma may affect distribution of uterine blood flow with consequent fetal growth restriction is biologically plausible. The objective of this study was to evaluate the association between the presence of one or more retroplacental leiomyomas, identified on routine second trimester ultrasound assessment, and fetal growth. METHODS
We conducted a retrospective cohort study to assess the effect of having one or more retroplacental leiomyomas on fetal birth weight and the incidence of small for gestational age infants among women with singleton pregnancies undergoing routine second trimester fetal anatomic ultrasound at our institution between 2007 and 2012. Specialized obstetric and gynaecologic sonographers Figure 1. Ultrasound image showing a 6.2 cm right fundal retroplacental leiomyoma (RPL) adjacent to the placenta (P), identified on routine second trimester anatomic surveillance ultrasound
performed the ultrasound examinations. Final diagnoses and interpretations were determined by one of four attending maternal-fetal medicine physicians. In accordance with the American Institute of Ultrasound in Medicine guidelines for obstetric ultrasound examination,9 the presence, location, and size of all leiomyomas were recorded. In women with leiomyomas, data on leiomyoma number, size, location in the uterus, and location relative to the placenta were collected. Leiomyoma size was recorded using the largest diameter measured. We reviewed medical records to obtain maternal demographic data and medical comorbidities. Women who delivered outside our primary health care system were excluded from the analysis. Potential confounding factors for birth weight were identified as gestational diabetes, preexisting diabetes, chronic hypertension, and maternal tobacco use. Gestational diabetes was defined as a plasma glucose level of more than 7.8 mmol/L on a one-hour screening glucose challenge test followed by at least two abnormal values on a three-hour glucose tolerance test using the National Diabetes Data Group limit.10 Pre-gestational diabetes was defined as either type I or type II diabetes mellitus diagnosed before pregnancy. Chronic hypertension was defined as a systolic blood pressure of 140 mm Hg or a diastolic blood pressure of 90 mm Hg before 20 weeks of gestation or the use of antihypertensive medications before pregnancy. Delivery records were obtained from the Riverside Methodist Hospital medical record database. The primary outcomes were birth weight and the incidence of SGA, defined as a birth weight less than the 10th percentile for gestational age.11 Descriptive statistics were used to estimate the frequency of leiomyomas in the study population. The control group was randomly selected from patients without an ICD-9 diagnostic code for leiomyomas who were registered in the OhioHealth database for 2007e2012 and who underwent a routine second trimester anatomical ultrasound examination and delivered at an OhioHealth facility at a gestational age greater than 24 weeks (Figure 2). This control group was generated with a systemic random sampling method in order to obtain a sample size equivalent to the case group. Baseline demographic and medical characteristics of women with retroplacental leiomyomas were compared with women without leiomyomas using chi-square tests and student t tests. Multivariable linear and logistic regression analyses controlling for gestational age at
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Figure 2. Study flowchart Second trimester ultrasound paents 2007-2012
Cases ICD-9 leiomyoma (n = 453) Controls
> 1 Documented Retroplacental leiomyomata
No ICD-9 leiomyoma (n = 189)
(n = 172) Excluded (n = 31)
Excluded (n = 48)
Incomplete data: Prenatal history (n = 22) Delivery outcomes (n = 9)
Incomplete data: Prenatal history (n = 40) Delivery outcomes (n = 8) Cases
Controls
Complete records available
Complete records available
(n = 141)
(n = 141)
delivery, age, ethnicity, BMI, and medical comorbidities including chronic hypertension, gestational diabetes, and pre-existing diabetes were conducted to determine if retroplacental location was associated with altered birth weight and SGA. A separate linear regression analysis was conducted to identify the potential effect of number and size of leiomyoma. Statistical significance was based on traditional two-sided tests with the alpha error set at 5%. Statistical analyses were conducted using SPSS Statistics version 19.0 (IBM Corp., Armonk, NY).
Women with retroplacental leiomyomas were older, more likely to be African-American, and were more likely to have a higher BMI than those without leiomyomas. Gravidity, parity, and the incidence of other medical comorbidities (including gestational and pre-existing diabetes and chronic and gestational hypertension) were similar in both groups. Gestational age at delivery was significantly less in women with retroplacental leiomyomas than in women without leiomyomas (38.1 weeks vs. 39.2 weeks, P < 0.026), as was birth weight (3114.4 g vs. 3366.6 g, P < 0.001) (Table 1).
Ethics approval for the study was obtained from the Riverside Methodist Hospital/OhioHealth Institutional Review Board.
Birth weight, controlled for gestational age at delivery, was 177 g less in women with retroplacental leiomyoma than in women without leiomyomas (95% CI 295 g to 95 g, P ¼ 0.003).
RESULTS
A total of 14 156 women underwent routine second trimester ultrasound assessment at our institution between 2007 and 2012. The incidence of leiomyoma was 4.0% (n ¼ 453). Of women with documented leiomyomas, 38% had at least one retroplacental leiomyoma (n ¼ 172). Complete obstetric data, including prenatal history and delivery outcome, were available for 141 of these women (82%).
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After controlling for gestational age at delivery, there was a non-significant trend towards a higher incidence of SGA infants in women with retroplacental leiomyomas (n ¼ 22) compared with women without leiomyomas (n ¼ 9) (OR 2.58, 95% CI 0.97 to 6.84, P ¼ 0.057). Of the 141 women with retroplacental leiomyomas, 17 (12%) had a leiomyoma > 10 cm, 65 (46%) had a leiomyoma measuring between 4 cm and 10 cm, and 58 women (41%) had a leiomyoma measuring < 4 cm. The mean diameter of leiomyomas in
Effect of Maternal Retroplacental Leiomyomas on Fetal Growth
Age in years
Retroplacental leiomyoma (n ¼ 141)
No leiomyoma (n ¼ 141)
34.2 (4.4)
31.5 (5.2)
Race/ethnicity
Pa <0.001 0.955
Caucasian
76
77
African American
47
31.2
Hispanic
4
6
Asian
5
4
Other
9
10
2.6 (1.6)
2.8 (1.6)
0.347
Parity
0.9 (1.2)
1.3 (1.2)
0.004
Gestational age at delivery in daysb
270.1 (15.7)
273.5 (8.2)
0.026
Birth weight in grams
3114.4 (628.0)
3366.6 (494.7)
0.001
BMI in kg/m2
6.38% 4.26% 1.42%
29.4 (8.0)
27.3 (7.1)
Mulple leiomyomas
Retroplacental leiomyoma < 4cm
Retroplacental leiomyoma > 4cm
DISCUSSION
Comorbidities (n)
0.023 1.000
Chorioamnionitis
1
0
Gestational hypertension
1
1
Chronic hypertension
9
9
Gestational diabetes
7
7
Pre-existing diabetes
3
3
Data are mean ± standard deviation unless otherwise specified. a P for comparison of women with retroplacental leiomyoma compared with women with no leiomyoma.
Based on ultrasound dating.
women with retroplacental leiomyomas was 5.05 cm (Table 2). Women with a retroplacental leiomyoma > 4 cm were more likely to have an SGA infant (n ¼ 16) than women without a leiomyoma (n ¼ 9) (OR 2.84, 95% CI 1.01 to 8.01, P ¼ 0.048) (Figure 3). The maximum number of retroplacental leiomyomas detected in an individual woman was three; the median number was one (130 women had 1, 9 women had 2, and 2 women had 3). There was no difference in birth weight between pregnant women with multiple retroplacental leiomyomas and pregnant women without leiomyoma (P ¼ 0.623). Table 2. Leiomyoma characteristics in pregnant women with retroplacental leiomyoma Characteristica Mean width in cm (SD)
5.01 (2.6)
Mean height in cm (SD)
5.05 (5.2)
Mean number of leiomyomas (SD)
1.1 (0.2)
a
11.35%
No leiomyoma
Gravidity
b
Figure 3. Proportion of SGA infants in pregnant women with no leiomyomas, multiple leiomyomas, and retroplacental leiomyomas
Percentage of SGA Infants
Table 1. Characteristics of pregnant women with retroplacental leiomyomas and pregnant women without leiomyomas
Leiomyoma size was determined by the largest diameter identified on ultrasound.
Infants born to women with one or more retroplacental leiomyomas have significantly lower birth weights than infants born to women without leiomyomas. Specifically, after controlling for gestational age at delivery and for other significant confounders including age, BMI, and maternal medical comorbities (chronic hypertension, gestational diabetes, and pre-existing diabetes), women with retroplacental leiomyomas were more likely to deliver an infant that was SGA than women without leiomyomas, although this trend did not reach statistical significance. However, retroplacental leiomyomas > 4 cm in maximal diameter were significantly associated with SGA. The mechanisms by which retroplacental leiomyomas increase the risk of low birth weight infants are unknown, but may include inflammation, alterations in the endometrium, and revascularization with redistribution of uterine blood flow. A previous study of leiomyoma size and number indicate that adverse obstetric outcomes including increased risk of low birth weight may be attributable to a global uterine effect.1 However, other studies have shown conflicting data regarding leiomyoma location and the relationship of leiomyomas to fetal growth.3,4 Our study is unique because it only compared women with retroplacental leiomyomas to women without leiomyomas. In this comparison, the increased rate of SGA infants suggests that the location of leiomyoma in relation to the placenta may have an impact on fetal growth, and that direct physical interaction between the placenta and the leiomyoma may increase the risk of low birth weight more than the global vascular effect of leiomyomas.1 However, this can only be speculated because we did not compare outcomes in women with retroplacental leiomyomas with
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outcomes in women with leiomyomas not located beneath the placental implantation site.
REFERENCES
We found that women with a retroplacental leiomyoma > 4 cm in maximum diameter were at risk for having SGA infants; these women may therefore benefit from having increased fetal growth surveillance during pregnancy.
1. Stout MJ, Odibo AO, Graseck AS, Macones GA, Crane JP, Cahill AG. Leiomyomas at routine second trimester ultrasound examination and adverse obstetric outcomes. Obstet Gynecol 2011;116:1056e63.
A strength of this study was that it included a large population of women with retroplacental leiomyomas with few confounding variables. The prevalence of leiomyomas in our study population was 4%, which is similar to previous reports.1 Limitations of the study include its retrospective nature, which inherently introduces bias. Although this study focused on the primary outcome of birth weight at delivery, future prospective studies should address other neonatal outcomes (e.g., admission to NICU, respiratory distress syndrome, length of NICU stay) to emphasize the clinical importance of identifying SGA infants.
3. Sheiner E, Bashiri A, Levy A, Hershkovitz R, Katz M, Mazor M. Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. J Repro Med 2004;49:182e6.
CONCLUSION
As women delay childbearing to their later reproductive years, the incidence of leiomyomas during pregnancy increases. The clinical effects of leiomyomas in pregnancy must be discussed in prenatal and antepartum counselling. We found that retroplacental leiomyomas are associated with decreased birth weight, and consequently increased fetal surveillance may be beneficial in women with this common uterine finding.
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2. Chen YH, Lin HC. Increased risk of preterm births among women with uterine leiomyoma: a nationwide population-based study. Hum Reprod 2009;24:3049e56.
4. Coronado GD, Marshall LM, Schwartz SM. Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population based study. Obstet Gynecol 2000;95:764e9. 5. Qidwai GI, Caughey AB, Jacoby AF. Obstetric outcomes in women with sonographically identified uterine leiomyomata. Obstet Gynecol 2006;107:376e82. 6. Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyomas in pregnancy. Am J Obstet Gynecol 1989;160:1212e6. 7. Davis JL, Ray-Mazumder S, Hobel CJ, Baley K, Sassoon D. Uterine leiomyomas in pregnancy: a prospective study. Obstet Gynecol 1990;75:41e4. 8. Katz VL, Dotters DJ, Droegemeuller W. Complications of uterine leiomyomas in pregnancy. Obstet Gynecol 1989;73:593e6. 9. American Institute of Ultrasound in Medicine. Practice guideline. Obstetric Ultrasound. Laurel (MD): American Institute of Ultrasound in Medicine; 2007. 10. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23:S4e19. 11. Alexander GR, Himes JH, Kaufman RB, Mor O, Kogan M. A United States National reference for fetal growth. Obstet Gynecol 1996;87:163e8.