The Journal of Maternal-Fetal & Neonatal Medicine
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Small for gestational age newborns – does prerecognition make a difference in pregnancy outcome? Amir Aviram, Yariv Yogev, Ron Bardin, Israel Meizner, Arnon Wiznitzer & Eran Hadar To cite this article: Amir Aviram, Yariv Yogev, Ron Bardin, Israel Meizner, Arnon Wiznitzer & Eran Hadar (2015) Small for gestational age newborns – does pre-recognition make a difference in pregnancy outcome?, The Journal of Maternal-Fetal & Neonatal Medicine, 28:13, 1520-1524, DOI: 10.3109/14767058.2014.961912 To link to this article: http://dx.doi.org/10.3109/14767058.2014.961912
Published online: 26 Sep 2014.
Submit your article to this journal
Article views: 54
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [Chinese University of Hong Kong]
Date: 05 November 2015, At: 19:52
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(13): 1520–1524 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.961912
ORIGINAL ARTICLE
Small for gestational age newborns – does pre-recognition make a difference in pregnancy outcome? Amir Aviram1,2, Yariv Yogev1,2, Ron Bardin1,2, Israel Meizner1,2, Arnon Wiznitzer1,2, and Eran Hadar1,2 Rabin Medical Center, Helen Schneider Hospital for Women, Petah Tikva, Israel and 2Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
1
Abstract
Keywords
Objective: We aimed to evaluate whether pre-recognition of small for gestational age (SGA) at late preterm or term pregnancies, has an impact on pregnancy outcome. Methods: Retrospective analysis of SGA newborns, stratified to those with suspected or unsuspected IUGR according the sonographic estimated fetal weight (EFW), below the 10th percentile for gestational age (n ¼ 619), with fetuses not suspected as SGA (EFW 10th percentile) preformed up to 7 days prior to delivery (n ¼ 1770). Results: SGA was correctly diagnosed prior to delivery in 26% of the fetuses. Women with suspected SGA were delivered earlier (37.9 ± 1.7 versus 38.8 ± 1.4 weeks, p50.001) and at a lower birth weight (2280 ± 321 versus 2454 ± 263 grams, p50.001). They also had higher rates of induction of labor (19.1% versus 6.2%, p50.001) and cesarean delivery (29.1% versus 19.8%, p50.001). Fetuses suspected for SGA had higher rate of neonatal adverse outcome, but on multivariate analysis suspected SGA (aOR 0.41, 95% CI 0.20–0.86), birthweight (aOR 0.67, 95% CI 0.5 to 0.77 for each additional 50 g), gestational age at delivery (aOR 0.63, 95% CI 0.56–0.71 for each additional week) and spontaneous vaginal delivery (aOR 0.88, 95% CI 0.19–3.89) were independently associated with an improved neonatal composite outcome. Conclusion: Identification of SGA may improve neonatal outcome. However, by itself, it is not an indication for intervention, which may lead to adverse outcome.
Adverse pregnancy outcome, small for gestational age, sonographic estimated fetal weight, ultrasound
Introduction Small for gestational age (SGA) is a major contributor for perinatal morbidity and mortality [1] as for long term consequences in adulthood [2]. SGA is commonly defined as birthweight below the 10th percentile for gestational age at delivery. However, if antepartum suspicion of a small baby arises, it should be referred to as Fetal Growth Restriction (FGR) and not SGA, a term reserved for newborns [3]. Some of these small fetuses are growing normally within their genetic growth potential – i.e. constitutionally small, while the clinically significant sub-group includes those who are not fulfilling their genetic potential, due to various causes such as placental insufficiency, intra-uterine infections, congenital anomalies, genetic disorders and other possible etiologies [3]. Clinical and sonographic methods for fetal weight evaluation are imprecise [4,5] as is the determination of the cutoff for FGR and SGA, based upon several available growth curves [6–8].
Address for correspondence: Yariv Yogev, Helen Schneider Hospital for Women, Rabin Medical Center, Petach-Tikva 49100, Israel. Tel: +972-39377400. Fax: +972-3-9377409. E-mail: [email protected]
History Received 9 August 2014 Revised 29 August 2014 Accepted 2 September 2014 Published online 25 September 2014
Following the presumed diagnosis of FGR, the proper management is controversial [9]. Since there is no direct therapy for FGR, management is usually directed for recognizing the appropriate timing for delivery. This strategy is aimed to avoid mortality, improve morbidity and minimize the possible complications of interventions aimed to expedite birth. There is lack of evidence as to the optimal timing for delivery and the appropriate care until delivery. Therefore, the decision to deliver is individually tailored according to several considerations such as: gestational age, suspected etiology, severity of growth restriction, Doppler studies and fetal wellbeing [10–13]. Controversy exists whether antepartum identification of SGA is associated with improved neonatal outcome or unnecessary interventions [14–18]. Therefore, we aimed to evaluate whether pre-recognition of SGA at late preterm or term pregnancies, has an impact on pregnancy outcome.
Methods We conducted a retrospective cohort analysis of SGA newborns, stratified to those with suspected or unsuspected antepartum growth restriction in order to compare maternal, fetal and neonatal outcomes between the groups. The study was approved by the local institutional review board.
Pre-recognition of SGA
DOI: 10.3109/14767058.2014.961912
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
Study population We included in the study all the women who delivered in a single, tertiary, university affiliated medical center, from July 2008 to December 2013. Eligibility was limited to women with a singleton pregnancy, at or beyond 34 weeks of gestation, with an actual birthweight below the 10th percentile for gestational age at delivery. Terminations of pregnancy and post-term pregnancies beyond 42 weeks of gestation were excluded. Maternal and perinatal outcome of pregnancies were compared between fetuses who were suspected as being growth restricted according to the sonographic estimated fetal weight (EFW), below the 10th percentile for gestational age, performed up to 7 days prior to delivery (n ¼ 619), with fetuses not suspected as SGA, defined as those without an available sonographic EFW or with an available sonographic EFW 10th percentile for gestational age, preformed up to 7 days prior to delivery (n ¼ 1770). Data collection Data was retrieved from the comprehensive computerized databases of the delivery room and ultrasound unit, and was cross-tabulated using an individualized identification number per patient. Data from the neonatal unit and the Neonatal Intensive Care Unit (NICU) were integrated into the delivery room database using the unique admission number assigned to each parturient and her offspring. Collected data included demographical as well as obstetrical data, sonographic biometric measurements, labor and delivery data and neonatal outcome. Definitions All biometric measurements were performed in a specialized obstetrical ultrasound unit by senior physicians who are wellexperienced in sonography, or by experienced ultrasound technicians. Sonographic EFW was calculated using the Hadlcok formula [19]. Gestational age was determined based on maternally reported Last Menstrual Period (LMP) and was affirmed by the Crown-Ramp length (CRL) measured at a first trimester sonogram [20,21]. Term delivery was considered as delivery between 37 + 0/7 and 42 + 0/7 weeks of gestation. Late preterm delivery was defined as delivery between 34 + 0/7 and 36 + 6/7 weeks of gestation. Birth weight percentile was calculated using gender specific, national population based birth weight curves [6]. SGA was defined as birth weight below the 10th percentile for gestational age and FGR as a sonographic EFW below the 10th percentile for gestational age [3]. Diagnosis of gestational diabetes mellitus (GDM) was based Carpenter and Coustan criteria [22]. Hypertensive disorders were classified according to the International Society for the Study of Hypertension in Pregnancy guidelines [23]. Oligohydramnion and polyhydramnion were diagnosed when amniotic fluid volume measurements were below 50 mm or above 250 mm, respectively [24,25]. Minor perineal laceration was considered as grade 1 or 2 perineal tears or episiotomy, and major perineal trauma was defined as grade 3 or 4 perineal tears.
1521
Neonatal composite outcome was defined as one or more of the following diagnoses: NICU admission, Asphyxia, respiratory distress syndrome (RDS), sepsis, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), seizures, hemorrhagic ischemic encephalopathy (HIE), mechanical ventilation, meconium aspiration syndrome and neonatal death. Statistical analysis Statistical analysis was performed using the Statistical Package for Social Science Software (SPSS, version 21.0, IBM. Chicago, IL). Comparison between continuous variables was performed with Student’s t-test, and categorical data were compared using 2 test or Fisher’s exact test. Multivariate logistic regression and adjusted odds ratios were calculated where appropriate. A probability value below 0.05 was considered significant. The first analysis was used to determine the fundamental differences between both groups. A multivariate logistic regression model was used to ascertain the impact of different variable on the composite neonatal outcome. Using Epi-InfoÔ [26] and our perinatal database, our sample size was sufficient to detect odds ratio of 1.5 for composite neonatal outcome.
Results During the study period, 44 263 women delivered in our institution, of which 2389 (5.4%) women met the inclusion criteria. Out of this cohort, 619 (25.9%) were suspected as SGA prior to delivery and comprised the study group, and 1770 (74.1%) were not suspected as SGA and were diagnosed only after delivery (Table 1). When the actual birthweight was below the 3rd percentile for gestational age at delivery, the rate of pre-delivery suspected SGA was 35% and in the subgroup of women with recognized risk factors for SGA (hypertensive disorders, oligohydramnion and APLA) the rate of pre-delivery suspected SGA was 43%. Demographic and obstetrical characteristics Demographic and obstetrical characteristics, for the study and control groups, are presented in Table 1. The rates of maternal underlying disease and pregnancy complications were more prevalent in the study group, including: antiphospholipid antibody (APLS) syndrome (p ¼ 0.002), chronic hypertension (p50.001), mild preeclampsia (p ¼ 0.004), GDM and oligohydramnion (p50.001 for both). Labor and delivery outcome The rate of induction of labor was approximately 3-fold higher in the suspected SGA group (p50.001), while mean birth weight, mean birth weight percentiles and gestational age at delivery, in this group, were all slightly but significantly lower (p50.001 for all). The rate of spontaneous vaginal delivery was lower in the suspected SGA group (p50.001). Cesarean delivery rate as well as non-elective cesarean delivery rate were higher in the suspected SGA group (p50.001 for both), mostly due to non-reassuring
1522
A. Aviram et al.
J Matern Fetal Neonatal Med, 2015; 28(13): 1520–1524
fetal heart rate (p ¼ 0.03), prolonged 1st stage of labor (p ¼ 0.04) and breech presentation (p ¼ 0.007). The rate of minor perineal tear was lower in the suspected SGA group, as was the rate of meconium stained amniotic fluid (Table 2).
Table 1. Demographic and obstetrical characteristics for suspected and unsuspected SGA newborns.
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
Variable Maternal age, (years) Gravidity Parity Nulliparity Previous cesarean delivery Hypertensive disorders: Gestational hypertension Chronic hypertension Mild preeclampsia Severe preeclampsia Antiphospholipid antibody syndrome Diabetes mellitus: Gestational Pre-gestational Oligohydramnion Polyhydramnion Stillbirth
Suspected SGA (n ¼ 619)
Unsuspected SGA (n ¼ 1770)
p value
30.6 ± 5.3 2.5 ± 1.8 2.0 ± 1.3 305 (49.3) 56 (9.0)
30.2 ± 5.4 2.4 ± 1.6 2.0 ± 1.3 849 (48.0) 149 (8.4)
0.08 0.20 0.90 0.58 0.63
7 18 21 12 6
(1.1) (2.9) (3.4) (1.9) (1.0)
16 15 27 20 2
(0.9) (0.6) (1.5) (1.1) (0.1)
0.62 50.001 0.004 0.13 0.002
Neonatal outcome Neonatal and perinatal outcomes are presented in Table 3. The suspected SGA group was characterized by higher rates of NICU admission (p50.001), hypoglycemia (p ¼ 0.006), necrotizing enterocolitis (p ¼ 0.03), neonatal sepsis (p50.001), meconium aspiration syndrome (p ¼ 0.049), jaundice (p50.001), major cardiac anomalies (p ¼ 0.001) and a composite neonatal outcome (p50.001). On multivariate logistic regression model (Table 4), accounting for potential confounders, the factors that remained significantly associated with an adverse composite neonatal outcome were: suspected SGA (adjusted odds ratio 0.41, 95% CI 0.20–0.86), actual birthweight (aOR 0.67, 95% CI 0.58–0.77 for each additional 50 g), gestational age at delivery (aOR 0.63, 95% CI 0.56–0.71 for each additional week), spontaneous vaginal delivery (aOR 0.88, 95% CI 0.193.89), birth weight percentile53% for gestational age (aOR 2.43, 95% CI 1.86–3.17), mild preeclampsia (aOR 4.9, 95% CI 1.3–18.3), APLA syndrome (aOR 0.03, 95% CI 0.02–0.43) and major cardiac anomalies (aOR 4.81, 95% 1.39–16.62).
Discussion 41 (6.6) 2(0.4) 114 (18.4) 3 (0.5) 2 (0.3)
57 2 147 11 12
(3.2) (0.1) (8.3) (0.6) (0.7)
50.001 0.77 50.001 0.70 0.32
Data presented as n (%) or mean ± 1 standard deviation. SGA – small for gestational age.
We conducted a retrospective analysis of 2389 women delivering a SGA baby, stratified to those with suspected diagnosis of SGA prior to delivery and those with unsuspected SGA in which diagnosis was established only after delivery. Our main findings were: (1) SGA was correctly diagnosed prior to delivery in only 26% of the fetuses.
Table 2. Labor and delivery outcome for suspected and unsuspected SGA newborns.
Variable Labor induction Epidural analgesia Gestational age at delivery, weeks Late preterm birth (34–37 weeks) Birth weight, grams Birth weight percentile for gestational age, % Birth weight percentile 5 3% for gestational age Male gender Meconium stained amniotic fluid Spontaneous vaginal delivery Operative vaginal delivery, overall: For non-reassuring fetal heart rate For prolonged 2nd stage Cesarean delivery: Overall Non-elective* Indications for cesarean delivery Previous cesarean delivery Non reassuring fetal heart rate Prolonged 1st stage Prolonged 2nd stage Placental abruption Breech presentation Other indications Trial of labor after cesarean delivery Vaginal birth after cesarean delivery Perineal trauma: Minor perineal tear 3rd and 4th perineal tear
Suspected SGA (n ¼ 619)
Unsuspected SGA (n ¼ 1770)
p value
118 (19.1) 354 (57.2) 37.9 ± 1.7 116 (18.7) 2280 ± 321 5.4 ± 2.7 174 (28.1) 318 (51.4) 53 (8.6) 376 (60.7) 63 (10.2) 25 (4.0) 38 (6.1)
110 (6.2) 1011 (57.1) 38.8 ± 1.4 130 (7.3) 2454 ± 263 6.2 ± 2.7 312 (17.6) 902 (51.0) 216 (12.2) 1242 (70.2) 178 (10.1) 67 (3.8) 111 (6.3)
50.001 0.98 50.001 50.001 50.001 50.001 50.001 0.86 0.01 50.001 0.93 0.78 0.91
180 (29.1) 161 (89.4) 31 45 22 5 6 49 14 30 27
350 (19.8) 265 (75.7)
(5.0) (7.3) (3.6) (0.8) (1.0) (7.9) (2.3) (4.8) (4.4)
174 (28.1) 1 (0.2)
80 88 37 9 14 88 13 92 80
50.001 50.001
(4.5) (5.0) (2.1) (0.5) (0.8) (5.0) (0.7) (5.2) (4.5)
0.62 0.03 0.04 0.4 0.68 0.007 0.002 0.73 0.87
603 (34.1) 3 (0.2)
0.006 0.97
Data presented as n(%) or mean ± 1 standard deviation. SGA – small for gestational age. *Percentage out of cesarean deliveries.
Pre-recognition of SGA
DOI: 10.3109/14767058.2014.961912
Table 3. Neonatal outcome for suspected and unsuspected SGA newborns.
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
Variable 1-Min Apgar score 5 7 5-Min Apgar score 5 7 Neonatal Intensive Care Unit admission Neonatal Death Asphyxia Seizures Hypoxic ischemic encephalopathy Intraventricular Hemorrhage Umbilical cord pH57.2 Hypoglycemia Respiratory distress syndrome Necrotizing enterocolitis Sepsis Mechanical ventilation Meconium aspiration Jaundice Phototherapy Major anomalies: Cardiac system Central nervous system Skeletal system Digestive system Composite outcome
Suspected SGA (n ¼ 619)
Unsuspected SGA (n ¼ 1770)
p value
35 (5.7) 7 (1.1) 123 (19.9)
102 (5.8) 30 (1.7) 217 (12.3)
0.92 0.33 50.001
2 19 5 5
(0.3) (3.1) (0.8) (0.8)
12 55 6 6
(0.5) (3.1) (0.3) (0.3)
0.32 0.96 0.14 0.14
2 3 42 0 8 99 12 0 105 49
(0.3) (0.5) (6.8) (0) (1.3) (16.0) (1.9) (0) (17.0) (7.9)
9 18 72 2 8 173 33 11 202 87
(0.5) (1.0) (4.1) (0.1) (0.5) (9.8) (1.9) (0.6) (11.4) (4.9)
0.56 0.22 0.006 0.40 0.03 50.001 0.91 0.049 50.001 0.006
42 7 49 30 156
(6.8) (1.1) (7.9) (4.8) (23.6)
65 9 145 61 271
(3.7) (0.5) (8.2) (3.4) (15.3)
0.001 0.1 0.83 0.12 50.001
Data are presented as n(%) or mean ± 1 standard deviation. SGA – small for gestational age; Composite outcome – NICU admission, asphyxia, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, seizures, sepsis, mechanical ventilation, meconium aspiration syndrome, neonatal death. Table 4. Multivariate analysis of composite neonatal outcome.
Variable Suspected SGA Birth weight (each additional 50 g) Birth weight percentile 53% for gestational age Cesarean delivery Spontaneous vaginal delivery Gestational age at delivery (each additional week) Chronic hypertension Mild preeclampsia Gestational diabetes mellitus Antiphospholipid antibody syndrome Oligohydramnion Induction of labor Meconium aspiration syndrome Cardiac anomaly Skeletal anomaly Urological or gastrointestinal anomaly CNS anomaly
Adjusted 95% Confidence odds ratio interval p value 0.41 0.67 2.43
0.2–0.86 0.58–0.77 1.86–3.17
0.02 50.001 50.001
0.88 0.48 0.63
0.19–3.89 0.24–0.96 0.56–0.71
0.86 0.04 50.001
2.85 4.9 1.44 0.03 0.96 1.53 2.1 4.81 0.18 2.76 0.46
0.24–33.58 1.3–18.3 0.27–7.84 0.02–0.43 0.29–3.22 0.49–4.75 0.37–11.89 1.39–16.62 0.02–1.93 0.59–12.71 0.02–9.84
0.4 0.02 0.7 0.01 0.95 0.46 0.39 0.01 0.16 0.19 0.62
SGA – small for gestational age; CNS – central nervous systems; Composite outcome – NICU admission, asphyxia, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, seizures, sepsis, mechanical ventilation, meconium aspiration syndrome, neonatal death.
In those that were diagnosed we found a higher rate of hypertensive disorders, APLS and oligohydramnion. (2) Women with suspected SGA were delivered earlier and at a lower birth weight. They also had higher rates of induction of
1523
labor, lower rates of spontaneous vaginal delivery, higher rates of cesarean delivery and higher rates of non-elective cesarean delivery due to NRFHR or prolonged 1st stage of labor. (3) Fetuses suspected of SGA had a higher rate of neonatal adverse outcome. But on multivariate analysis suspected SGA, higher birthweight, higher gestational age at delivery and spontaneous vaginal delivery were independently associated with an improved neonatal composite outcome. Screening for SGA is usually accomplished by means of fundus-symphysis height assessment, clinical EFW or by abdominal palpation [27,28]. Diagnosis is based upon sonographic EFW or abdominal circumference, which can be selective (according to risk factors or upon clinical suspicion) or universal (usually at 30–32 weeks of gestation). All these methods demonstrate a low yield for SGA identification, with a sensitivity of approximately 50% [29–31]. In our cohort a single universal sonographic EFW is recommended routinely for all women at 31–33 weeks of gestation, but if a clinical suspicion arises or due to recognized risk factors the estimation is performed earlier and repeated every 2–3 weeks throughout gestation. In an aim to improve SGA detection it may be prudent do adopt a policy of multiple ultrasound measurement [32] or a late 3rd trimester sonographic EFW [33] with cutoffs set by a customized growth curve [34]. Importantly, those with relevant risk factors should be referred to fetal sonographic weight evaluation, to improve detection of accompanying SGA. The data on the association between antenatal diagnosis of growth restriction to adverse pregnancy and neonatal outcome are controversial [14–18]. Previous studies report that those identified as SGA prior to delivery have higher rates of interventions such as labor inductions [20,21] and both emergency and elective CS [14–17]. Some suggest that is not accompanied with and improved neonatal outcome [15,16], but rather only earlier gestational age at delivery [15,16] and a lower actual birthweight [15]. Conversely, recent studies demonstrate that SGA identification may lead to improved neonatal composite outcome [14,17,18], including individual components such as NICU admission, low 5-minute Apgar, low umbilical artery pH, hypoxic ischemic encephalopathy (HIE), cerebral palsy, mental retardation, stillbirth and infant death. Our study, in accordance with others [20,21,22,24], also suggests a higher rate of interventions for those identified as SGA, by labor induction and CS, as well as a mild decrease in gestational age at birth, higher rates of late preterm deliveries, lower birthweight and lower birthweight percentiles [15,16]. In terms of neonatal outcome, although those with antepartum recognized SGA have a higher rate of several neonatal complications, our multivariate analysis suggested that recognition of SGA is actually an independent protective factor from the neonatal composite outcome, and that induction of labor is not associated with an improved neonatal outcome. Therefore we suggest that SGA recognition leads to unwarranted intervention that do not have a favorable impact on neonatal outcome, and that the improvement in neonatal outcome is due to the diagnosis of SGA and implementing proper follow-up. This follow up allows
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
1524
A. Aviram et al.
conservative management and not premature unwarranted delivery. This is also supported by our multivariate analysis which demonstrated that each 50 g of additional birthweight and each additional week for gestational age at delivery were also independently protective from neonatal composite outcome. Therefore we suggest that induction of labor causes iatrogenic complications and does improve neonatal outcome, as similarly suggested by randomized trials as well [35]. Our study has some limitations due to lack of information on the etiology of SGA, mainly we could not extract Doppler data on those suspected with SGA as well as the indications for labor inductions. Moreover, due to the retrospective nature of the study, data regarding maternal BMI and Bishop score were lacking. Also, antiphospholipid antibody syndrome was not evaluated in all patients, rather only in some. Thus, it is expected that the prevalence would be increased among those with known SGA. In conclusion, identification of SGA may improve neonatal outcome. However, by itself, it is not an indication for delivery; moreover, initiated labor may lead to unnecessary interventions and iatrogenic complications. Therefore, diagnosing FGR should prompt further workup, aimed to elucidate the specific sub-groups of SGA that will benefit from induction. A tailored approach is needed depending upon etiology, weight percentiles, fetal status and other possible factors.
J Matern Fetal Neonatal Med, 2015; 28(13): 1520–1524
13. 14. 15. 16.
17.
18. 19. 20.
21. 22. 23.
Declaration of interest The authors declare no conflict of interests. 24.
References 1. McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999;340:1234–8. 2. Barker DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol 2006;49:270–83. 3. American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 134: fetal growth restriction. Obstet Gynecol 2013;121:1122–33. 4. Chauhan SP, Cole J, Sanderson M, et al. Suspicion of intrauterine growth restriction: use of abdominal circumference alone or estimated fetal weight below 10%. J Matern Fetal Neonatal Med 2006;19:557–62. 5. Bricker L, Mahsud-Dornan S, Dornan JC. Detection of foetal growth restriction using third trimester ultrasound. Best Pract Res Clin Obstet Gynaecol. 2009;23:833–44. 6. Dollberg S, Haklai Z, Mimouni FB, et al. Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005;7:311–14. 7. Chauhan SP, Magann EF. Screening for fetal growth restriction. Clin Obstet Gynecol 2006;49:284–94. 8. Falo AP. Intrauterine growth retardation (IUGR): prenatal diagnosis by imaging. Pediatr Endocrinol Rev 2009;6:326–31. 9. Vergani P, Roncaglia N, Ghidini A, et al. Can adverse neonatal outcome be predicted in late preterm or term fetal growth restriction? Ultrasound Obstet Gynecol 2010;36:166–70. 10. Hershkovitz R, Kingdom JC, Geary M, Rodeck CH. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2000;15:209–12. 11. Oros D, Figueras F, Cruz-Martinez R, Meler E, et al. Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2011;37:191–5. 12. DIGITAT Study Group. Which intrauterine growth restricted fetuses at term benefit from early labour induction? A secondary
25. 26. 27.
28. 29.
30.
31. 32. 33. 34. 35.
analysis of the DIGITAT randomised trial. Eur J Obstet Gynecol Reprod Biol 2014;172:20–5. GRIT Study Group. A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. BJOG 2003;110:27–32. Verlijsdonk JW, Winkens B, Boers K, et al. Suspected versus nonsuspected small-for-gestational age fetuses at term: perinatal outcomes. J Matern Fetal Neonatal Med 2012;25:938–43. Ohel G, Ruach M. Perinatal outcome of idiopathic small for gestational age pregnancies at term: the effect of antenatal diagnosis. Int J Gynaecol Obstet 1996;55:29–32. Jahn A, Razum O, Berle P. Routine screening for intrauterine growth retardation in Germany: low sensitivity and questionable benefit for diagnosed cases. Acta Obstet Gynecol Scand. 1998;77: 643–8. Fratelli N, Valcamonico A, Prefumo F, et al. Effects of antenatal recognition and follow-up on perinatal outcomes in smallfor- gestational age infants delivered after 36 weeks. Acta Obstet Gynecol Scand 2013;92:223–9. Lindqvist PG, Molin J. Does antenatal identification of smallfor-gestational age fetuses significantly improve their outcome? Ultrasound Obstet Gynecol 2005;25:258–64. Hadlock FP, Deter RL, Ronald BR, Seung KP. Estimation fetal age: computer assisted analysis of multiple fetal growth parameters. Radiology 1984;152:497–501. Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crownrump length: reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US. Radiology 1992;182: 501–5. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 101: ultrasonography in pregnancy. Obstet Gynecol 2009; 113:451–61. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768–73. Brown MA, Lindheimer MD, de Swiet M, et al. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;20:ix–xiv. Rutherford SE, Phelan JP, Smith CV, Jacobs N. The four-quadrant assessment of amniotic fluid volume: an adjunct to antepartum fetal heart rate testing. Obstet Gynecol 1987;70:353–6. Phelan JP, Ahn MO, Smith CV, et al. Amniotic fluid index measurements during pregnancy. J Reprod Med 1987;32:601–4. Epi-Info. Available from: http://www.openepi.com/v37/ SampleSize/SSCohort.htm. Lindhard A, Nielsen PV, Mouritsen LA, et al. The implications of introducing the symphyseal-fundal height-measurement: a prospective randomized controlled trial. Br J Obstet Gynaecol 1990; 97:675–80. Persson B, Stangenberg M, Lunell NO, et al. Prediction of size of infants at birth by measurement of symphysis fundus height. Br J Obstet Gynaecol 1986;93:206–11. David C, Tagliavini G, Pilu G, et al. Receiver-operator characteristic curves for the ultrasonographic prediction of smallfor-gestational-age fetuses in low-risk pregnancies. Am J Obstet Gynecol 1996;174:1037–42. De Reu PA, Smits LJ, Oosterbaan HP, Nijhuis JG. Value of a single early third trimester fetal biometry for the prediction of birth weight deviations in a low risk population. J Perinat Med 2008;36:324–9. Ben-Haroush A, Yogev Y, Hod M, Bar J. Predictive value of a single early fetal weight estimate in normal pregnancies. Eur J Obstet Gynecol Reprod Biol 2007;130:187–92. Hedriana HL, Moore TR. A comparison of single versus multiple growth ultrasonographic examinations in predicting birth weight. Am J Obstet Gynecol 1994;170:1600–4. Peregrine E, O’Brien P, Jauniaux E. Clinical and ultrasound estimation of birth weight prior to induction of labor at term. Ultrasound Obstet Gynecol 2007;29:304–9. De Jong CL, Francis A, Van Geijn HP, Gardosi J. Customized fetal weight limits for antenatal detection of fetal growth restriction. Ultrasound Obstet Gynecol 2000;15:36–40. DIGITAT Study Group. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ 2010;341:c7087.
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Small for gestational age newborns – does prerecognition make a difference in pregnancy outcome? Amir Aviram, Yariv Yogev, Ron Bardin, Israel Meizner, Arnon Wiznitzer & Eran Hadar To cite this article: Amir Aviram, Yariv Yogev, Ron Bardin, Israel Meizner, Arnon Wiznitzer & Eran Hadar (2015) Small for gestational age newborns – does pre-recognition make a difference in pregnancy outcome?, The Journal of Maternal-Fetal & Neonatal Medicine, 28:13, 1520-1524, DOI: 10.3109/14767058.2014.961912 To link to this article: http://dx.doi.org/10.3109/14767058.2014.961912
Published online: 26 Sep 2014.
Submit your article to this journal
Article views: 54
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [Chinese University of Hong Kong]
Date: 05 November 2015, At: 19:52
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(13): 1520–1524 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.961912
ORIGINAL ARTICLE
Small for gestational age newborns – does pre-recognition make a difference in pregnancy outcome? Amir Aviram1,2, Yariv Yogev1,2, Ron Bardin1,2, Israel Meizner1,2, Arnon Wiznitzer1,2, and Eran Hadar1,2 Rabin Medical Center, Helen Schneider Hospital for Women, Petah Tikva, Israel and 2Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
1
Abstract
Keywords
Objective: We aimed to evaluate whether pre-recognition of small for gestational age (SGA) at late preterm or term pregnancies, has an impact on pregnancy outcome. Methods: Retrospective analysis of SGA newborns, stratified to those with suspected or unsuspected IUGR according the sonographic estimated fetal weight (EFW), below the 10th percentile for gestational age (n ¼ 619), with fetuses not suspected as SGA (EFW 10th percentile) preformed up to 7 days prior to delivery (n ¼ 1770). Results: SGA was correctly diagnosed prior to delivery in 26% of the fetuses. Women with suspected SGA were delivered earlier (37.9 ± 1.7 versus 38.8 ± 1.4 weeks, p50.001) and at a lower birth weight (2280 ± 321 versus 2454 ± 263 grams, p50.001). They also had higher rates of induction of labor (19.1% versus 6.2%, p50.001) and cesarean delivery (29.1% versus 19.8%, p50.001). Fetuses suspected for SGA had higher rate of neonatal adverse outcome, but on multivariate analysis suspected SGA (aOR 0.41, 95% CI 0.20–0.86), birthweight (aOR 0.67, 95% CI 0.5 to 0.77 for each additional 50 g), gestational age at delivery (aOR 0.63, 95% CI 0.56–0.71 for each additional week) and spontaneous vaginal delivery (aOR 0.88, 95% CI 0.19–3.89) were independently associated with an improved neonatal composite outcome. Conclusion: Identification of SGA may improve neonatal outcome. However, by itself, it is not an indication for intervention, which may lead to adverse outcome.
Adverse pregnancy outcome, small for gestational age, sonographic estimated fetal weight, ultrasound
Introduction Small for gestational age (SGA) is a major contributor for perinatal morbidity and mortality [1] as for long term consequences in adulthood [2]. SGA is commonly defined as birthweight below the 10th percentile for gestational age at delivery. However, if antepartum suspicion of a small baby arises, it should be referred to as Fetal Growth Restriction (FGR) and not SGA, a term reserved for newborns [3]. Some of these small fetuses are growing normally within their genetic growth potential – i.e. constitutionally small, while the clinically significant sub-group includes those who are not fulfilling their genetic potential, due to various causes such as placental insufficiency, intra-uterine infections, congenital anomalies, genetic disorders and other possible etiologies [3]. Clinical and sonographic methods for fetal weight evaluation are imprecise [4,5] as is the determination of the cutoff for FGR and SGA, based upon several available growth curves [6–8].
Address for correspondence: Yariv Yogev, Helen Schneider Hospital for Women, Rabin Medical Center, Petach-Tikva 49100, Israel. Tel: +972-39377400. Fax: +972-3-9377409. E-mail: [email protected]
History Received 9 August 2014 Revised 29 August 2014 Accepted 2 September 2014 Published online 25 September 2014
Following the presumed diagnosis of FGR, the proper management is controversial [9]. Since there is no direct therapy for FGR, management is usually directed for recognizing the appropriate timing for delivery. This strategy is aimed to avoid mortality, improve morbidity and minimize the possible complications of interventions aimed to expedite birth. There is lack of evidence as to the optimal timing for delivery and the appropriate care until delivery. Therefore, the decision to deliver is individually tailored according to several considerations such as: gestational age, suspected etiology, severity of growth restriction, Doppler studies and fetal wellbeing [10–13]. Controversy exists whether antepartum identification of SGA is associated with improved neonatal outcome or unnecessary interventions [14–18]. Therefore, we aimed to evaluate whether pre-recognition of SGA at late preterm or term pregnancies, has an impact on pregnancy outcome.
Methods We conducted a retrospective cohort analysis of SGA newborns, stratified to those with suspected or unsuspected antepartum growth restriction in order to compare maternal, fetal and neonatal outcomes between the groups. The study was approved by the local institutional review board.
Pre-recognition of SGA
DOI: 10.3109/14767058.2014.961912
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
Study population We included in the study all the women who delivered in a single, tertiary, university affiliated medical center, from July 2008 to December 2013. Eligibility was limited to women with a singleton pregnancy, at or beyond 34 weeks of gestation, with an actual birthweight below the 10th percentile for gestational age at delivery. Terminations of pregnancy and post-term pregnancies beyond 42 weeks of gestation were excluded. Maternal and perinatal outcome of pregnancies were compared between fetuses who were suspected as being growth restricted according to the sonographic estimated fetal weight (EFW), below the 10th percentile for gestational age, performed up to 7 days prior to delivery (n ¼ 619), with fetuses not suspected as SGA, defined as those without an available sonographic EFW or with an available sonographic EFW 10th percentile for gestational age, preformed up to 7 days prior to delivery (n ¼ 1770). Data collection Data was retrieved from the comprehensive computerized databases of the delivery room and ultrasound unit, and was cross-tabulated using an individualized identification number per patient. Data from the neonatal unit and the Neonatal Intensive Care Unit (NICU) were integrated into the delivery room database using the unique admission number assigned to each parturient and her offspring. Collected data included demographical as well as obstetrical data, sonographic biometric measurements, labor and delivery data and neonatal outcome. Definitions All biometric measurements were performed in a specialized obstetrical ultrasound unit by senior physicians who are wellexperienced in sonography, or by experienced ultrasound technicians. Sonographic EFW was calculated using the Hadlcok formula [19]. Gestational age was determined based on maternally reported Last Menstrual Period (LMP) and was affirmed by the Crown-Ramp length (CRL) measured at a first trimester sonogram [20,21]. Term delivery was considered as delivery between 37 + 0/7 and 42 + 0/7 weeks of gestation. Late preterm delivery was defined as delivery between 34 + 0/7 and 36 + 6/7 weeks of gestation. Birth weight percentile was calculated using gender specific, national population based birth weight curves [6]. SGA was defined as birth weight below the 10th percentile for gestational age and FGR as a sonographic EFW below the 10th percentile for gestational age [3]. Diagnosis of gestational diabetes mellitus (GDM) was based Carpenter and Coustan criteria [22]. Hypertensive disorders were classified according to the International Society for the Study of Hypertension in Pregnancy guidelines [23]. Oligohydramnion and polyhydramnion were diagnosed when amniotic fluid volume measurements were below 50 mm or above 250 mm, respectively [24,25]. Minor perineal laceration was considered as grade 1 or 2 perineal tears or episiotomy, and major perineal trauma was defined as grade 3 or 4 perineal tears.
1521
Neonatal composite outcome was defined as one or more of the following diagnoses: NICU admission, Asphyxia, respiratory distress syndrome (RDS), sepsis, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), seizures, hemorrhagic ischemic encephalopathy (HIE), mechanical ventilation, meconium aspiration syndrome and neonatal death. Statistical analysis Statistical analysis was performed using the Statistical Package for Social Science Software (SPSS, version 21.0, IBM. Chicago, IL). Comparison between continuous variables was performed with Student’s t-test, and categorical data were compared using 2 test or Fisher’s exact test. Multivariate logistic regression and adjusted odds ratios were calculated where appropriate. A probability value below 0.05 was considered significant. The first analysis was used to determine the fundamental differences between both groups. A multivariate logistic regression model was used to ascertain the impact of different variable on the composite neonatal outcome. Using Epi-InfoÔ [26] and our perinatal database, our sample size was sufficient to detect odds ratio of 1.5 for composite neonatal outcome.
Results During the study period, 44 263 women delivered in our institution, of which 2389 (5.4%) women met the inclusion criteria. Out of this cohort, 619 (25.9%) were suspected as SGA prior to delivery and comprised the study group, and 1770 (74.1%) were not suspected as SGA and were diagnosed only after delivery (Table 1). When the actual birthweight was below the 3rd percentile for gestational age at delivery, the rate of pre-delivery suspected SGA was 35% and in the subgroup of women with recognized risk factors for SGA (hypertensive disorders, oligohydramnion and APLA) the rate of pre-delivery suspected SGA was 43%. Demographic and obstetrical characteristics Demographic and obstetrical characteristics, for the study and control groups, are presented in Table 1. The rates of maternal underlying disease and pregnancy complications were more prevalent in the study group, including: antiphospholipid antibody (APLS) syndrome (p ¼ 0.002), chronic hypertension (p50.001), mild preeclampsia (p ¼ 0.004), GDM and oligohydramnion (p50.001 for both). Labor and delivery outcome The rate of induction of labor was approximately 3-fold higher in the suspected SGA group (p50.001), while mean birth weight, mean birth weight percentiles and gestational age at delivery, in this group, were all slightly but significantly lower (p50.001 for all). The rate of spontaneous vaginal delivery was lower in the suspected SGA group (p50.001). Cesarean delivery rate as well as non-elective cesarean delivery rate were higher in the suspected SGA group (p50.001 for both), mostly due to non-reassuring
1522
A. Aviram et al.
J Matern Fetal Neonatal Med, 2015; 28(13): 1520–1524
fetal heart rate (p ¼ 0.03), prolonged 1st stage of labor (p ¼ 0.04) and breech presentation (p ¼ 0.007). The rate of minor perineal tear was lower in the suspected SGA group, as was the rate of meconium stained amniotic fluid (Table 2).
Table 1. Demographic and obstetrical characteristics for suspected and unsuspected SGA newborns.
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
Variable Maternal age, (years) Gravidity Parity Nulliparity Previous cesarean delivery Hypertensive disorders: Gestational hypertension Chronic hypertension Mild preeclampsia Severe preeclampsia Antiphospholipid antibody syndrome Diabetes mellitus: Gestational Pre-gestational Oligohydramnion Polyhydramnion Stillbirth
Suspected SGA (n ¼ 619)
Unsuspected SGA (n ¼ 1770)
p value
30.6 ± 5.3 2.5 ± 1.8 2.0 ± 1.3 305 (49.3) 56 (9.0)
30.2 ± 5.4 2.4 ± 1.6 2.0 ± 1.3 849 (48.0) 149 (8.4)
0.08 0.20 0.90 0.58 0.63
7 18 21 12 6
(1.1) (2.9) (3.4) (1.9) (1.0)
16 15 27 20 2
(0.9) (0.6) (1.5) (1.1) (0.1)
0.62 50.001 0.004 0.13 0.002
Neonatal outcome Neonatal and perinatal outcomes are presented in Table 3. The suspected SGA group was characterized by higher rates of NICU admission (p50.001), hypoglycemia (p ¼ 0.006), necrotizing enterocolitis (p ¼ 0.03), neonatal sepsis (p50.001), meconium aspiration syndrome (p ¼ 0.049), jaundice (p50.001), major cardiac anomalies (p ¼ 0.001) and a composite neonatal outcome (p50.001). On multivariate logistic regression model (Table 4), accounting for potential confounders, the factors that remained significantly associated with an adverse composite neonatal outcome were: suspected SGA (adjusted odds ratio 0.41, 95% CI 0.20–0.86), actual birthweight (aOR 0.67, 95% CI 0.58–0.77 for each additional 50 g), gestational age at delivery (aOR 0.63, 95% CI 0.56–0.71 for each additional week), spontaneous vaginal delivery (aOR 0.88, 95% CI 0.193.89), birth weight percentile53% for gestational age (aOR 2.43, 95% CI 1.86–3.17), mild preeclampsia (aOR 4.9, 95% CI 1.3–18.3), APLA syndrome (aOR 0.03, 95% CI 0.02–0.43) and major cardiac anomalies (aOR 4.81, 95% 1.39–16.62).
Discussion 41 (6.6) 2(0.4) 114 (18.4) 3 (0.5) 2 (0.3)
57 2 147 11 12
(3.2) (0.1) (8.3) (0.6) (0.7)
50.001 0.77 50.001 0.70 0.32
Data presented as n (%) or mean ± 1 standard deviation. SGA – small for gestational age.
We conducted a retrospective analysis of 2389 women delivering a SGA baby, stratified to those with suspected diagnosis of SGA prior to delivery and those with unsuspected SGA in which diagnosis was established only after delivery. Our main findings were: (1) SGA was correctly diagnosed prior to delivery in only 26% of the fetuses.
Table 2. Labor and delivery outcome for suspected and unsuspected SGA newborns.
Variable Labor induction Epidural analgesia Gestational age at delivery, weeks Late preterm birth (34–37 weeks) Birth weight, grams Birth weight percentile for gestational age, % Birth weight percentile 5 3% for gestational age Male gender Meconium stained amniotic fluid Spontaneous vaginal delivery Operative vaginal delivery, overall: For non-reassuring fetal heart rate For prolonged 2nd stage Cesarean delivery: Overall Non-elective* Indications for cesarean delivery Previous cesarean delivery Non reassuring fetal heart rate Prolonged 1st stage Prolonged 2nd stage Placental abruption Breech presentation Other indications Trial of labor after cesarean delivery Vaginal birth after cesarean delivery Perineal trauma: Minor perineal tear 3rd and 4th perineal tear
Suspected SGA (n ¼ 619)
Unsuspected SGA (n ¼ 1770)
p value
118 (19.1) 354 (57.2) 37.9 ± 1.7 116 (18.7) 2280 ± 321 5.4 ± 2.7 174 (28.1) 318 (51.4) 53 (8.6) 376 (60.7) 63 (10.2) 25 (4.0) 38 (6.1)
110 (6.2) 1011 (57.1) 38.8 ± 1.4 130 (7.3) 2454 ± 263 6.2 ± 2.7 312 (17.6) 902 (51.0) 216 (12.2) 1242 (70.2) 178 (10.1) 67 (3.8) 111 (6.3)
50.001 0.98 50.001 50.001 50.001 50.001 50.001 0.86 0.01 50.001 0.93 0.78 0.91
180 (29.1) 161 (89.4) 31 45 22 5 6 49 14 30 27
350 (19.8) 265 (75.7)
(5.0) (7.3) (3.6) (0.8) (1.0) (7.9) (2.3) (4.8) (4.4)
174 (28.1) 1 (0.2)
80 88 37 9 14 88 13 92 80
50.001 50.001
(4.5) (5.0) (2.1) (0.5) (0.8) (5.0) (0.7) (5.2) (4.5)
0.62 0.03 0.04 0.4 0.68 0.007 0.002 0.73 0.87
603 (34.1) 3 (0.2)
0.006 0.97
Data presented as n(%) or mean ± 1 standard deviation. SGA – small for gestational age. *Percentage out of cesarean deliveries.
Pre-recognition of SGA
DOI: 10.3109/14767058.2014.961912
Table 3. Neonatal outcome for suspected and unsuspected SGA newborns.
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
Variable 1-Min Apgar score 5 7 5-Min Apgar score 5 7 Neonatal Intensive Care Unit admission Neonatal Death Asphyxia Seizures Hypoxic ischemic encephalopathy Intraventricular Hemorrhage Umbilical cord pH57.2 Hypoglycemia Respiratory distress syndrome Necrotizing enterocolitis Sepsis Mechanical ventilation Meconium aspiration Jaundice Phototherapy Major anomalies: Cardiac system Central nervous system Skeletal system Digestive system Composite outcome
Suspected SGA (n ¼ 619)
Unsuspected SGA (n ¼ 1770)
p value
35 (5.7) 7 (1.1) 123 (19.9)
102 (5.8) 30 (1.7) 217 (12.3)
0.92 0.33 50.001
2 19 5 5
(0.3) (3.1) (0.8) (0.8)
12 55 6 6
(0.5) (3.1) (0.3) (0.3)
0.32 0.96 0.14 0.14
2 3 42 0 8 99 12 0 105 49
(0.3) (0.5) (6.8) (0) (1.3) (16.0) (1.9) (0) (17.0) (7.9)
9 18 72 2 8 173 33 11 202 87
(0.5) (1.0) (4.1) (0.1) (0.5) (9.8) (1.9) (0.6) (11.4) (4.9)
0.56 0.22 0.006 0.40 0.03 50.001 0.91 0.049 50.001 0.006
42 7 49 30 156
(6.8) (1.1) (7.9) (4.8) (23.6)
65 9 145 61 271
(3.7) (0.5) (8.2) (3.4) (15.3)
0.001 0.1 0.83 0.12 50.001
Data are presented as n(%) or mean ± 1 standard deviation. SGA – small for gestational age; Composite outcome – NICU admission, asphyxia, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, seizures, sepsis, mechanical ventilation, meconium aspiration syndrome, neonatal death. Table 4. Multivariate analysis of composite neonatal outcome.
Variable Suspected SGA Birth weight (each additional 50 g) Birth weight percentile 53% for gestational age Cesarean delivery Spontaneous vaginal delivery Gestational age at delivery (each additional week) Chronic hypertension Mild preeclampsia Gestational diabetes mellitus Antiphospholipid antibody syndrome Oligohydramnion Induction of labor Meconium aspiration syndrome Cardiac anomaly Skeletal anomaly Urological or gastrointestinal anomaly CNS anomaly
Adjusted 95% Confidence odds ratio interval p value 0.41 0.67 2.43
0.2–0.86 0.58–0.77 1.86–3.17
0.02 50.001 50.001
0.88 0.48 0.63
0.19–3.89 0.24–0.96 0.56–0.71
0.86 0.04 50.001
2.85 4.9 1.44 0.03 0.96 1.53 2.1 4.81 0.18 2.76 0.46
0.24–33.58 1.3–18.3 0.27–7.84 0.02–0.43 0.29–3.22 0.49–4.75 0.37–11.89 1.39–16.62 0.02–1.93 0.59–12.71 0.02–9.84
0.4 0.02 0.7 0.01 0.95 0.46 0.39 0.01 0.16 0.19 0.62
SGA – small for gestational age; CNS – central nervous systems; Composite outcome – NICU admission, asphyxia, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, seizures, sepsis, mechanical ventilation, meconium aspiration syndrome, neonatal death.
In those that were diagnosed we found a higher rate of hypertensive disorders, APLS and oligohydramnion. (2) Women with suspected SGA were delivered earlier and at a lower birth weight. They also had higher rates of induction of
1523
labor, lower rates of spontaneous vaginal delivery, higher rates of cesarean delivery and higher rates of non-elective cesarean delivery due to NRFHR or prolonged 1st stage of labor. (3) Fetuses suspected of SGA had a higher rate of neonatal adverse outcome. But on multivariate analysis suspected SGA, higher birthweight, higher gestational age at delivery and spontaneous vaginal delivery were independently associated with an improved neonatal composite outcome. Screening for SGA is usually accomplished by means of fundus-symphysis height assessment, clinical EFW or by abdominal palpation [27,28]. Diagnosis is based upon sonographic EFW or abdominal circumference, which can be selective (according to risk factors or upon clinical suspicion) or universal (usually at 30–32 weeks of gestation). All these methods demonstrate a low yield for SGA identification, with a sensitivity of approximately 50% [29–31]. In our cohort a single universal sonographic EFW is recommended routinely for all women at 31–33 weeks of gestation, but if a clinical suspicion arises or due to recognized risk factors the estimation is performed earlier and repeated every 2–3 weeks throughout gestation. In an aim to improve SGA detection it may be prudent do adopt a policy of multiple ultrasound measurement [32] or a late 3rd trimester sonographic EFW [33] with cutoffs set by a customized growth curve [34]. Importantly, those with relevant risk factors should be referred to fetal sonographic weight evaluation, to improve detection of accompanying SGA. The data on the association between antenatal diagnosis of growth restriction to adverse pregnancy and neonatal outcome are controversial [14–18]. Previous studies report that those identified as SGA prior to delivery have higher rates of interventions such as labor inductions [20,21] and both emergency and elective CS [14–17]. Some suggest that is not accompanied with and improved neonatal outcome [15,16], but rather only earlier gestational age at delivery [15,16] and a lower actual birthweight [15]. Conversely, recent studies demonstrate that SGA identification may lead to improved neonatal composite outcome [14,17,18], including individual components such as NICU admission, low 5-minute Apgar, low umbilical artery pH, hypoxic ischemic encephalopathy (HIE), cerebral palsy, mental retardation, stillbirth and infant death. Our study, in accordance with others [20,21,22,24], also suggests a higher rate of interventions for those identified as SGA, by labor induction and CS, as well as a mild decrease in gestational age at birth, higher rates of late preterm deliveries, lower birthweight and lower birthweight percentiles [15,16]. In terms of neonatal outcome, although those with antepartum recognized SGA have a higher rate of several neonatal complications, our multivariate analysis suggested that recognition of SGA is actually an independent protective factor from the neonatal composite outcome, and that induction of labor is not associated with an improved neonatal outcome. Therefore we suggest that SGA recognition leads to unwarranted intervention that do not have a favorable impact on neonatal outcome, and that the improvement in neonatal outcome is due to the diagnosis of SGA and implementing proper follow-up. This follow up allows
The Journal of Maternal-Fetal & Neonatal Medicine 2015.28:1520-1524.
1524
A. Aviram et al.
conservative management and not premature unwarranted delivery. This is also supported by our multivariate analysis which demonstrated that each 50 g of additional birthweight and each additional week for gestational age at delivery were also independently protective from neonatal composite outcome. Therefore we suggest that induction of labor causes iatrogenic complications and does improve neonatal outcome, as similarly suggested by randomized trials as well [35]. Our study has some limitations due to lack of information on the etiology of SGA, mainly we could not extract Doppler data on those suspected with SGA as well as the indications for labor inductions. Moreover, due to the retrospective nature of the study, data regarding maternal BMI and Bishop score were lacking. Also, antiphospholipid antibody syndrome was not evaluated in all patients, rather only in some. Thus, it is expected that the prevalence would be increased among those with known SGA. In conclusion, identification of SGA may improve neonatal outcome. However, by itself, it is not an indication for delivery; moreover, initiated labor may lead to unnecessary interventions and iatrogenic complications. Therefore, diagnosing FGR should prompt further workup, aimed to elucidate the specific sub-groups of SGA that will benefit from induction. A tailored approach is needed depending upon etiology, weight percentiles, fetal status and other possible factors.
J Matern Fetal Neonatal Med, 2015; 28(13): 1520–1524
13. 14. 15. 16.
17.
18. 19. 20.
21. 22. 23.
Declaration of interest The authors declare no conflict of interests. 24.
References 1. McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999;340:1234–8. 2. Barker DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol 2006;49:270–83. 3. American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 134: fetal growth restriction. Obstet Gynecol 2013;121:1122–33. 4. Chauhan SP, Cole J, Sanderson M, et al. Suspicion of intrauterine growth restriction: use of abdominal circumference alone or estimated fetal weight below 10%. J Matern Fetal Neonatal Med 2006;19:557–62. 5. Bricker L, Mahsud-Dornan S, Dornan JC. Detection of foetal growth restriction using third trimester ultrasound. Best Pract Res Clin Obstet Gynaecol. 2009;23:833–44. 6. Dollberg S, Haklai Z, Mimouni FB, et al. Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005;7:311–14. 7. Chauhan SP, Magann EF. Screening for fetal growth restriction. Clin Obstet Gynecol 2006;49:284–94. 8. Falo AP. Intrauterine growth retardation (IUGR): prenatal diagnosis by imaging. Pediatr Endocrinol Rev 2009;6:326–31. 9. Vergani P, Roncaglia N, Ghidini A, et al. Can adverse neonatal outcome be predicted in late preterm or term fetal growth restriction? Ultrasound Obstet Gynecol 2010;36:166–70. 10. Hershkovitz R, Kingdom JC, Geary M, Rodeck CH. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2000;15:209–12. 11. Oros D, Figueras F, Cruz-Martinez R, Meler E, et al. Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2011;37:191–5. 12. DIGITAT Study Group. Which intrauterine growth restricted fetuses at term benefit from early labour induction? A secondary
25. 26. 27.
28. 29.
30.
31. 32. 33. 34. 35.
analysis of the DIGITAT randomised trial. Eur J Obstet Gynecol Reprod Biol 2014;172:20–5. GRIT Study Group. A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. BJOG 2003;110:27–32. Verlijsdonk JW, Winkens B, Boers K, et al. Suspected versus nonsuspected small-for-gestational age fetuses at term: perinatal outcomes. J Matern Fetal Neonatal Med 2012;25:938–43. Ohel G, Ruach M. Perinatal outcome of idiopathic small for gestational age pregnancies at term: the effect of antenatal diagnosis. Int J Gynaecol Obstet 1996;55:29–32. Jahn A, Razum O, Berle P. Routine screening for intrauterine growth retardation in Germany: low sensitivity and questionable benefit for diagnosed cases. Acta Obstet Gynecol Scand. 1998;77: 643–8. Fratelli N, Valcamonico A, Prefumo F, et al. Effects of antenatal recognition and follow-up on perinatal outcomes in smallfor- gestational age infants delivered after 36 weeks. Acta Obstet Gynecol Scand 2013;92:223–9. Lindqvist PG, Molin J. Does antenatal identification of smallfor-gestational age fetuses significantly improve their outcome? Ultrasound Obstet Gynecol 2005;25:258–64. Hadlock FP, Deter RL, Ronald BR, Seung KP. Estimation fetal age: computer assisted analysis of multiple fetal growth parameters. Radiology 1984;152:497–501. Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crownrump length: reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US. Radiology 1992;182: 501–5. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 101: ultrasonography in pregnancy. Obstet Gynecol 2009; 113:451–61. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768–73. Brown MA, Lindheimer MD, de Swiet M, et al. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;20:ix–xiv. Rutherford SE, Phelan JP, Smith CV, Jacobs N. The four-quadrant assessment of amniotic fluid volume: an adjunct to antepartum fetal heart rate testing. Obstet Gynecol 1987;70:353–6. Phelan JP, Ahn MO, Smith CV, et al. Amniotic fluid index measurements during pregnancy. J Reprod Med 1987;32:601–4. Epi-Info. Available from: http://www.openepi.com/v37/ SampleSize/SSCohort.htm. Lindhard A, Nielsen PV, Mouritsen LA, et al. The implications of introducing the symphyseal-fundal height-measurement: a prospective randomized controlled trial. Br J Obstet Gynaecol 1990; 97:675–80. Persson B, Stangenberg M, Lunell NO, et al. Prediction of size of infants at birth by measurement of symphysis fundus height. Br J Obstet Gynaecol 1986;93:206–11. David C, Tagliavini G, Pilu G, et al. Receiver-operator characteristic curves for the ultrasonographic prediction of smallfor-gestational-age fetuses in low-risk pregnancies. Am J Obstet Gynecol 1996;174:1037–42. De Reu PA, Smits LJ, Oosterbaan HP, Nijhuis JG. Value of a single early third trimester fetal biometry for the prediction of birth weight deviations in a low risk population. J Perinat Med 2008;36:324–9. Ben-Haroush A, Yogev Y, Hod M, Bar J. Predictive value of a single early fetal weight estimate in normal pregnancies. Eur J Obstet Gynecol Reprod Biol 2007;130:187–92. Hedriana HL, Moore TR. A comparison of single versus multiple growth ultrasonographic examinations in predicting birth weight. Am J Obstet Gynecol 1994;170:1600–4. Peregrine E, O’Brien P, Jauniaux E. Clinical and ultrasound estimation of birth weight prior to induction of labor at term. Ultrasound Obstet Gynecol 2007;29:304–9. De Jong CL, Francis A, Van Geijn HP, Gardosi J. Customized fetal weight limits for antenatal detection of fetal growth restriction. Ultrasound Obstet Gynecol 2000;15:36–40. DIGITAT Study Group. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ 2010;341:c7087.
