J. Perinat. Med. 2015; 43(4): 485–492
Ioannis Papastefanou*, Athena P. Souka, Makarios Eleftheriades, Athanasios Pilalis, Charalambos Chrelias and Dimitrios Kassanos
Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan Abstract Aim: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). Method: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. Results: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2 = 0.39) with BW1 being the strongest predictor (R2 = 0.37). The addition of EFW conferred significant improvement (R2 = 0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. Conclusions: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. *Corresponding author: Dr. Ioannis Papastefanou, 3rd Department of Obstetrics and Gynecology, “Attikon” University Hospital, Rimini 1, 124 62, Haidari, Athens, Greece, Tel.: +030-210-5832236, Fax: +030-210-5826447, E-mail: [email protected] Athena P. Souka and Athanasios Pilalis: Fetal Medicine Unit, 3rd Department of Obstetrics and Gynaecology, Athens Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece; and Fetal Medicine Unit, Leto Maternity Hospital, Athens, Greece Makarios Eleftheriades: Fetal Medicine Unit, Leto Maternity Hospital, Athens, Greece Ioannis Papastefanou, Charalambos Chrelias and Dimitrios Kassanos: Fetal Medicine Unit, 3rd Department of Obstetrics and Gynaecology, Athens Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece
Incorporating EFW enhanced the sensitivity for the detection of both conditions. Keywords: Birth weight (BW); large for gestational age (LGA); parity; small for gestational age (SGA); third trimester ultrasound. DOI 10.1515/jpm-2013-0308 Received November 11, 2013. Accepted May 23, 2014. Previously published online June 17, 2014.
Introduction Birth weight (BW) deviations are associated with significant perinatal mortality and morbidity and increased risk of disease in adult life [2, 6, 18, 20]. Several maternal factors have been identified to influence fetal growth patterns; parity and history of having small or large children are amongst the strongest. Large epidemiologic studies have shown that primiparae are at higher risk of delivering a small for gestational age (SGA) neonate in conjunction with hypertension/preeclampsia or not [4, 16, 28]. In parous women the outcome of the previous pregnancy is a strong predictive factor for SGA or large for gestational age (LGA) [1, 3, 7, 13, 17, 28, 34]. Besides, there is evidence of familial aggregation of SGA in that the risk of a woman to deliver a small child increases if she was born small herself or if her sister’s child was born small [17]. In clinical practice, screening for fetal growth deviation is performed either by symphysio fundal height (SFH) measurement or by third trimester ultrasound examination [23, 24, 31]. The SFH measurement has low sensitivity and specificity while the incorporation of maternal demographic characteristics (such as maternal height, weight, ethnicity, and parity) improves the performance of the test [8, 9, 15, 23]. Fetal biometry by third trimester ultrasound is probably more effective in predicting both
Unauthenticated Download Date | 4/27/16 8:14 PM
486 Papastefanou et al., Predicting fetal growth deviation in parous women SGA and LGA births [24, 31]. Combinations of maternal demographic characteristics (race, height, weight, parity, smoking, mode of conception), fetal biometric parameters (crown-rump length – CRL, nuchal translucency, abdominal circumference, estimated fetal weight – EFW), and maternal serum biochemical markers have been studied in the construction of models with the aim to predict fetal growth deviation [22, 24, 31]. Parity and history of SGA or LGA were significant factors in those models. A previous study has shown that the BW of previous siblings improved the prediction of BW in a subsequent pregnancy after adjustment for gestational age [29]. Another recent study concluded that women with a history of SGA in their first pregnancy have increased risk of SGA in the subsequent pregnancy [33]. However, previous studies did not combine history of SGA or BW of previous siblings with third trimester scan for the prediction of BW deviations in a subsequent pregnancy. In the present study, we examine the value of the BW of the previous pregnancy in predicting fetal growth deviation in the next pregnancy. We have used the z-scores of the BW of the previous pregnancy as a continuous variable in order to predict the BW of the following pregnancy. We also sought to elucidate the additional benefit confirmed by third trimester fetal biometry and fetal Doppler studies in the prediction of fetal growth deviations.
Methods This was a retrospective cohort study carried out at the Fetal Medicine Unit of a University Hospital and the Fetal Medicine Unit of a private Maternity Hospital between April 2006 and September 2011. A computer search identified low-risk singleton pregnancies that had a third trimester ultrasound examination after 30 weeks for fetal biometry and Doppler studies and known pregnancy outcome. All women are offered a routine third trimester growth scan with Doppler assessment according to our local protocol. The study population consisted of the subgroup of parous women with singleton pregnancies (index pregnancies) in which details of the previous delivery/deliveries were recorded. The BW of the last delivery prior to the index pregnancy (BW1) and the BW in the index pregnancy (BW2) were used for the analysis. All women were offered a nuchal scan at 11–14 weeks of gestation and an anomaly scan at 20–24 weeks of gestation. Gestational age was based on the first day of the last normal menstrual period and confirmed by first trimester ultrasound scan (nuchal scan). Ultrasound age estimates in the first trimester were based on CRL measurements. Sonographic age by CRL was used to adjust the menstrual age if there was more than a 1-week discrepancy between menstrual dating and sonographic assessment. Third trimester ultrasound examination included the following biometric parameters: bi-parietal diameter, head circumference (calculated by bi-parietal diameter and occipito-frontal diameter measurements), abdominal circumference (calculated by anteriorposterior and trans-abdominal diameter measurements), and femur
length. The EFW was calculated by the Hadlock formula [11]. Color Doppler was used to identify the umbilical artery and the middle cerebral artery and measure the pulsatility index (UA-PI and MCA-PI, respectively). Care was taken to obtain fetal Doppler signals in the absence of fetal and breathing movements; three consecutive cardiac cycles were recorded in order to measure the pulsatility indices. In pregnancies with more than one ultrasound examination, the first one was considered for the analysis. Parity was defined as a previous delivery at or beyond 24 weeks of gestation. Maternal weight and height, smoking status (smoker or nonsmoker), mode of conception (spontaneous or assisted conception), and third trimester ultrasound scan parameters were recorded in a computer database (Astraia software; Astraia GmbH, Munich, Germany). We excluded pregnancies with chromosomally and/or structurally abnormal fetuses, pregnancies resulting in intra-uterine death or pregnancies diagnosed with severe early onset growth restriction prior to 30 weeks of gestation, and pregnancies with diabetes and hypertensive disorders. All ultrasound scans were performed by sonographers with at least 3 years scanning experience. Pregnancy outcomes were obtained from the hospitals’ databases. The Ethics Committee of the two institutes approved the use of this data for analysis.
Statistical analysis Normality of the distributions was tested by the Shapiro–Francia test and skewed parameters were transformed to obtain Gaussian distributions required for the regression models. Normally distributed continuous parameters were compared by unpaired t-test whereas Mann-Whitney U-test was used for nonnormally distributed continuous variables. Dichotomous variables were compared by χ2-test. We used our recently published updated reference ranges for BW, EFW, and Doppler studies to adjust the examined parameters [32]. Subsequently BW z-scores for previous (z-BW1) and index pregnancies (z-BW2) were computed. Additionally we calculated z-scores for EFW (z-log10 EFW), UA-PI (z-UA-PI), and MCA-PI (z-MCA-PI) for the purpose of our analyses. We used separate reference ranges for BW and EFW because plotting EFW in BW charts could be highly misleading due to the over-presentation of IUGR in preterm deliveries [25, 32]. Thus the utilization of BW curves for EFW is not the appropriate methodology because the diagnosis of SGA could be missed [25, 32]. SGA was defined as BW ≤ 5th centile and LGA as BW ≥ 95th centile for gestational age. Multiple stepwise linear regression analysis with backward elimination was used for our analyses. Multiple Wald stepwise logistic regression analysis and receiving operation characteristic (ROC) curve analysis were applied to develop and evaluate the prediction models, respectively. Cook’s distances were used to identify influential outliers and residual diagnostics assessed the model’s fit for all regression analyses.
Results The study group consisted of 1298 parous women. The demographic characteristics and distributions of the examined parameters for the SGA and LGA subgroups are presented in Tables 1 and 2, respectively. Some 73 newborns
Unauthenticated Download Date | 4/27/16 8:14 PM
Papastefanou et al., Predicting fetal growth deviation in parous women 487 Table 1 Characteristics of the SGA group in the index pregnancy. Continuous variables are presented as median (SD) and dichotomous variables as number (%). Variable (n = 1298)
SGA (n = 73)
Weight (kg) Smoking status Assisted conception Gestational age at delivery (days) BW (g) Gestational age at ultrasound examination (days) z-BW2 z-UA z-MCA z-log10 EFW z-BW1
62 (12.7) 15 (20.5%) 0 266 (14.8) 2360 (385.2) 249 (16.2) –2.1 (0.6) 0.4 (4.1) –0.5 (0.99) –2.1 (1.3) –1.6 (1.3)
Non-SGA (n = 1225)
P-value
0.05 0.023 –
Ioannis Papastefanou*, Athena P. Souka, Makarios Eleftheriades, Athanasios Pilalis, Charalambos Chrelias and Dimitrios Kassanos
Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan Abstract Aim: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). Method: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. Results: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2 = 0.39) with BW1 being the strongest predictor (R2 = 0.37). The addition of EFW conferred significant improvement (R2 = 0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. Conclusions: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. *Corresponding author: Dr. Ioannis Papastefanou, 3rd Department of Obstetrics and Gynecology, “Attikon” University Hospital, Rimini 1, 124 62, Haidari, Athens, Greece, Tel.: +030-210-5832236, Fax: +030-210-5826447, E-mail: [email protected] Athena P. Souka and Athanasios Pilalis: Fetal Medicine Unit, 3rd Department of Obstetrics and Gynaecology, Athens Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece; and Fetal Medicine Unit, Leto Maternity Hospital, Athens, Greece Makarios Eleftheriades: Fetal Medicine Unit, Leto Maternity Hospital, Athens, Greece Ioannis Papastefanou, Charalambos Chrelias and Dimitrios Kassanos: Fetal Medicine Unit, 3rd Department of Obstetrics and Gynaecology, Athens Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece
Incorporating EFW enhanced the sensitivity for the detection of both conditions. Keywords: Birth weight (BW); large for gestational age (LGA); parity; small for gestational age (SGA); third trimester ultrasound. DOI 10.1515/jpm-2013-0308 Received November 11, 2013. Accepted May 23, 2014. Previously published online June 17, 2014.
Introduction Birth weight (BW) deviations are associated with significant perinatal mortality and morbidity and increased risk of disease in adult life [2, 6, 18, 20]. Several maternal factors have been identified to influence fetal growth patterns; parity and history of having small or large children are amongst the strongest. Large epidemiologic studies have shown that primiparae are at higher risk of delivering a small for gestational age (SGA) neonate in conjunction with hypertension/preeclampsia or not [4, 16, 28]. In parous women the outcome of the previous pregnancy is a strong predictive factor for SGA or large for gestational age (LGA) [1, 3, 7, 13, 17, 28, 34]. Besides, there is evidence of familial aggregation of SGA in that the risk of a woman to deliver a small child increases if she was born small herself or if her sister’s child was born small [17]. In clinical practice, screening for fetal growth deviation is performed either by symphysio fundal height (SFH) measurement or by third trimester ultrasound examination [23, 24, 31]. The SFH measurement has low sensitivity and specificity while the incorporation of maternal demographic characteristics (such as maternal height, weight, ethnicity, and parity) improves the performance of the test [8, 9, 15, 23]. Fetal biometry by third trimester ultrasound is probably more effective in predicting both
Unauthenticated Download Date | 4/27/16 8:14 PM
486 Papastefanou et al., Predicting fetal growth deviation in parous women SGA and LGA births [24, 31]. Combinations of maternal demographic characteristics (race, height, weight, parity, smoking, mode of conception), fetal biometric parameters (crown-rump length – CRL, nuchal translucency, abdominal circumference, estimated fetal weight – EFW), and maternal serum biochemical markers have been studied in the construction of models with the aim to predict fetal growth deviation [22, 24, 31]. Parity and history of SGA or LGA were significant factors in those models. A previous study has shown that the BW of previous siblings improved the prediction of BW in a subsequent pregnancy after adjustment for gestational age [29]. Another recent study concluded that women with a history of SGA in their first pregnancy have increased risk of SGA in the subsequent pregnancy [33]. However, previous studies did not combine history of SGA or BW of previous siblings with third trimester scan for the prediction of BW deviations in a subsequent pregnancy. In the present study, we examine the value of the BW of the previous pregnancy in predicting fetal growth deviation in the next pregnancy. We have used the z-scores of the BW of the previous pregnancy as a continuous variable in order to predict the BW of the following pregnancy. We also sought to elucidate the additional benefit confirmed by third trimester fetal biometry and fetal Doppler studies in the prediction of fetal growth deviations.
Methods This was a retrospective cohort study carried out at the Fetal Medicine Unit of a University Hospital and the Fetal Medicine Unit of a private Maternity Hospital between April 2006 and September 2011. A computer search identified low-risk singleton pregnancies that had a third trimester ultrasound examination after 30 weeks for fetal biometry and Doppler studies and known pregnancy outcome. All women are offered a routine third trimester growth scan with Doppler assessment according to our local protocol. The study population consisted of the subgroup of parous women with singleton pregnancies (index pregnancies) in which details of the previous delivery/deliveries were recorded. The BW of the last delivery prior to the index pregnancy (BW1) and the BW in the index pregnancy (BW2) were used for the analysis. All women were offered a nuchal scan at 11–14 weeks of gestation and an anomaly scan at 20–24 weeks of gestation. Gestational age was based on the first day of the last normal menstrual period and confirmed by first trimester ultrasound scan (nuchal scan). Ultrasound age estimates in the first trimester were based on CRL measurements. Sonographic age by CRL was used to adjust the menstrual age if there was more than a 1-week discrepancy between menstrual dating and sonographic assessment. Third trimester ultrasound examination included the following biometric parameters: bi-parietal diameter, head circumference (calculated by bi-parietal diameter and occipito-frontal diameter measurements), abdominal circumference (calculated by anteriorposterior and trans-abdominal diameter measurements), and femur
length. The EFW was calculated by the Hadlock formula [11]. Color Doppler was used to identify the umbilical artery and the middle cerebral artery and measure the pulsatility index (UA-PI and MCA-PI, respectively). Care was taken to obtain fetal Doppler signals in the absence of fetal and breathing movements; three consecutive cardiac cycles were recorded in order to measure the pulsatility indices. In pregnancies with more than one ultrasound examination, the first one was considered for the analysis. Parity was defined as a previous delivery at or beyond 24 weeks of gestation. Maternal weight and height, smoking status (smoker or nonsmoker), mode of conception (spontaneous or assisted conception), and third trimester ultrasound scan parameters were recorded in a computer database (Astraia software; Astraia GmbH, Munich, Germany). We excluded pregnancies with chromosomally and/or structurally abnormal fetuses, pregnancies resulting in intra-uterine death or pregnancies diagnosed with severe early onset growth restriction prior to 30 weeks of gestation, and pregnancies with diabetes and hypertensive disorders. All ultrasound scans were performed by sonographers with at least 3 years scanning experience. Pregnancy outcomes were obtained from the hospitals’ databases. The Ethics Committee of the two institutes approved the use of this data for analysis.
Statistical analysis Normality of the distributions was tested by the Shapiro–Francia test and skewed parameters were transformed to obtain Gaussian distributions required for the regression models. Normally distributed continuous parameters were compared by unpaired t-test whereas Mann-Whitney U-test was used for nonnormally distributed continuous variables. Dichotomous variables were compared by χ2-test. We used our recently published updated reference ranges for BW, EFW, and Doppler studies to adjust the examined parameters [32]. Subsequently BW z-scores for previous (z-BW1) and index pregnancies (z-BW2) were computed. Additionally we calculated z-scores for EFW (z-log10 EFW), UA-PI (z-UA-PI), and MCA-PI (z-MCA-PI) for the purpose of our analyses. We used separate reference ranges for BW and EFW because plotting EFW in BW charts could be highly misleading due to the over-presentation of IUGR in preterm deliveries [25, 32]. Thus the utilization of BW curves for EFW is not the appropriate methodology because the diagnosis of SGA could be missed [25, 32]. SGA was defined as BW ≤ 5th centile and LGA as BW ≥ 95th centile for gestational age. Multiple stepwise linear regression analysis with backward elimination was used for our analyses. Multiple Wald stepwise logistic regression analysis and receiving operation characteristic (ROC) curve analysis were applied to develop and evaluate the prediction models, respectively. Cook’s distances were used to identify influential outliers and residual diagnostics assessed the model’s fit for all regression analyses.
Results The study group consisted of 1298 parous women. The demographic characteristics and distributions of the examined parameters for the SGA and LGA subgroups are presented in Tables 1 and 2, respectively. Some 73 newborns
Unauthenticated Download Date | 4/27/16 8:14 PM
Papastefanou et al., Predicting fetal growth deviation in parous women 487 Table 1 Characteristics of the SGA group in the index pregnancy. Continuous variables are presented as median (SD) and dichotomous variables as number (%). Variable (n = 1298)
SGA (n = 73)
Weight (kg) Smoking status Assisted conception Gestational age at delivery (days) BW (g) Gestational age at ultrasound examination (days) z-BW2 z-UA z-MCA z-log10 EFW z-BW1
62 (12.7) 15 (20.5%) 0 266 (14.8) 2360 (385.2) 249 (16.2) –2.1 (0.6) 0.4 (4.1) –0.5 (0.99) –2.1 (1.3) –1.6 (1.3)
Non-SGA (n = 1225)
P-value
0.05 0.023 –
