http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(6): 705–708 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.929109
ORIGINAL ARTICLE
The effect of placental abruption on the outcome of extremely premature infants
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
Seishi Furukawa, Koutarou Doi, Ken Furuta, and Hiroshi Sameshima Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Abstract
Keywords
Objective: To determine the effect of placental abruption on the outcome of infants born between 22 and 26 weeks of gestation. Methods: A retrospective study involving 32 cases of placental abruption. Controls were matched to cases according to gestational age and birth weight. Medical records were reviewed to confirm maternal background and neonatal outcome. We compared characteristics of maternal background and neonatal outcome between the two groups. Results: There were no significant differences in the incidence of pregnancy-induced hypertension, low maternal fibrinogen (5200 mg/dl), premature rupture of membrane, intrauterine infection, ischemic changes of the placenta, or funisitis between the groups. Non-reassuring fetal heart rate patterns (NRFHRs) during intrapartum were frequently seen in the placental abruption group compared to controls (75% versus 51%, p ¼ 0.02). However, no differences were found for the incidence of low umbilical artery pH (57.1), cerebral palsy, or neonatal death. The incidence of chronic lung disease (CLD, 66% versus 43%, p ¼ 0.04) and hemosiderin deposition on the placenta (16% versus 0%, p50.01) was higher in abruptions compared to controls. Conclusion: Placental abruption has a risk for the development of NRFHRs and CLD in infants born between 22 and 26 weeks of gestation, but shows no effect on neonatal mortality.
Extremely premature infant, neonatal outcome, placental abruption
Introduction Placental abruption (abruption) is a major cause of poor perinatal outcome [1–3] and occurs in approximately 1% of all pregnancies [4,5]. It is well known that women diagnosed with abruption have a 4- to 6-fold increased risk of a preterm delivery [2]. In fact, the number of abruptions is almost equal in term and preterm births [6], and they are more common in cases involving a lower gestational age [7]. Thus, premature delivery with abruption is an important issue in perinatal care. Ananth et al. showed that gestation-specific perinatal mortality rates were similar between abruption and non-abruption births less than 28 weeks of gestational age [8]. This report suggested that extreme immaturity is a major contributing factor for poor prognosis in cases with a gestational age of less than 28 weeks. Unfortunately, this finding has been given little attention when considering the detailed prognosis of extremely premature infants born in situations involving abruption. However, one report regarding the influence of abruption on neonatal outcome in premature infants around 29 weeks of gestation indicated that a preterm
Address for correspondence: Seishi Furukawa, MD, Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. E-mail: [email protected]
History Received 20 November 2013 Accepted 26 May 2014 Published online 26 June 2014
birth due to abruption is the main determining factor for a poor prognosis [9]. Further studies are definitely needed. We therefore conducted a case–control study to compare the prognosis of infants delivered after abruption between 22 and 26 weeks of gestation with controls of matched gestational age and birth weight without abruption. The current study was conducted in the setting of a tertiary perinatal center with standardized care. We determined the impact of abruption on neonatal outcome of infants born between 22 and 26 weeks of gestation.
Materials and methods This study was conducted retrospectively and there was therefore no need to obtain approval from a suitably constituted Ethics Committee in our institution. We reviewed the medical charts of infants born at 2226 weeks of gestation and admitted to the Perinatal Center, University of Miyazaki, from January 2000 to April 2010. Gestational age was assessed on the basis of the last menstrual period and first-trimester ultrasound fetometry. Our center is the only tertiary perinatal center in the Miyazaki province of Japan. There are 11 000 births per year in the Miyazaki province and our neonatal center deals with over 90% of premature infants with a birth weight of less than 1000 g in our province.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
706
S. Furukawa et al.
We determined abruption by the presence of retro-placental hematoma and clinical presentations (any one or combination of genital bleeding, abdominal pain, pregnancy-induced hypertension (PIH), premature labor, premature rupture of membrane, intrauterine fetal death, or non-reassuring fetal heart rate pattern (NRFHR) [10,11]. Confirmation of retroplacental hematoma was made by visual examination after delivery. Evidence of hematoma immediately after detachment of the placenta was also regarded as a retro-placental hematoma. Cases fulfilling the following criteria were selected: infant living on delivery, a record of FHR on admission and intrapartum, presence of blood gas data for the umbilical artery, and neurodevelopmental assessment performed at an age of 1 year or older. Excluded from the study were cases involving multifetal pregnancy, fetal anomaly, and chromosomal abnormality. A total of 32 infants involving mothers with abruption were thus enrolled in this study. Controls were selected by identifying infants born without abruption within 1 week of the non-control gestational age and a birth weight of 50 g. Each case was matched with at least two controls. A total of 69 controls involving mothers without abruption were enrolled in this study. The following antenatal and intrapartum characteristics were collected: maternal age, parity (primipara), gestational age at birth, use of tocolytics (MgSO4, ritodrine hydrochloride), presence of hypertension, premature rupture of membranes (PROM), intrauterine infection, NRFHRs on admission and intrapartum, cesarean delivery, and decreased maternal fibrinogen (defined as 5200 mg/dl) as an indicator of coagulopathy. In our institution, tocolysis was first conducted with continuous intravenous administration of ritodrine hydrochloride with uterine contractions of four in 20 min or eight in 60 min with progressive changes of dilatation and/or effacement in the cervix. Fetal heart rate monitoring was also conducted to detect potential fetal hypoxia prior to the start of tocolysis. Tocolysis was stopped if fetal asphyxia was evident. If uterine contractions continued, magnesium sulfate was added. Antenatal corticosteroid treatment for mothers with preterm labor was not routinely given at our institution during the study period. In this study, hypertension included chronic hypertension and PIH. Chronic hypertension was defined as hypertension diagnosed prior to conception or within the first 20 weeks of pregnancy. PIH such as gestational hypertension, preeclampsia, eclampsia and superimposed preeclampsia was defined according to the classification of the National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy [12]. Intrauterine infection was defined according to whether the presence of bacteria in amniotic fluid was determined by amniocentesis or clinical chorioamnionitis. Clinical chorioamnionitis was defined as the presence of a maternal febrile condition (438 C), maternal tachycardia (4120 beats/min), maternal leukocytosis (415 000 cells/mm3), and an elevated CRP level (45.0 mg/dl). Fetal heart rate patterns were classified according to the NICHD guideline [13]. Cases of variable decelerations (VDs) were classified into mild, moderate (mVD), and severe (sVD) using Kubli’s classification [14]. In this study, NRFHRs included recurrent late deceleration, recurrent mVD, recurrent sVD, prolonged deceleration, or
J Matern Fetal Neonatal Med, 2015; 28(6): 705–708
bradycardia. The fibrinogen value of the mother was obtained at the day of delivery. The following neonatal characteristics were also collected: sex (boy/girl), birth weight (g), umbilical artery pH (UA pH), intrauterine growth restriction (IUGR), chronic lung disease (CLD), intraventricular hemorrhage (IVH) Grade 3, intestinal perforation, neonatal death (ND), and cerebral palsy (CP). IUGR was defined as a sex-specific birth weight less than the 10th percentile for gestational age according to the Japanese standard growth curve for singletons [15]. Neonatal cranial ultrasound examinations were performed by an attending physician using a 7.5-Hz transducer on admission and then routinely with a repeated examination twice every day until day 7, and weekly up to 1 month. If an attending physician detected IVH, the severity of the IVH was determined by at least two physicians. The grading of IVH follows that described by Papile et al. [16]. Intestinal perforation was diagnosed using clinical characteristics and operative findings [17]. CLD was defined as the need for oxygen supplement at postnatal day 28 or 36 corrected weeks, with positive radiographic findings. Independent pediatric neurologists who were blinded to the study performed the neurodevelopmental assessment of a child with CP. Assessment was performed at an age of 1 year or older. Pathologists in our institution conducted placental histopathological examinations. Gross and histological examination of the placenta and cord were performed, and results were recorded on a standardized form. The following attributes were obtained for each placenta: chorioamnionitis, funisitis, hemosiderin deposition, and ischemic changes. Funisitis was defined when neutrophils were diffusely present throughout the wall of at least one of the umbilical vessels. Ischemic changes included chorangiosis, increased syncytial knots, and atherosis of uteroplacental vessels. Data are expressed as number, incidence (%), or mean ± SD. Comparisons between groups were made using 2 tests. Probability values 50.05 were considered significant.
Results The mean gestational age at delivery in both groups was 24.2 weeks. A comparison of antenatal and intrapartum data between groups showed similarities for maternal age, parity, use of tocolytics, percentage of hypertension, PROM, intrauterine infection, cesarean delivery, and decreased maternal fibrinogen (Table 1). The percentage of NRFHRs on admission was similar between groups (19% versus 14%, p ¼ 0.59). However, the percentage of NRFHRs for intrapartum in the abruption group was significantly higher than that of controls (75% versus 51%, p ¼ 0.02). As shown in Table 2, the incidence of UA pH57.1, IUGR, intestinal perforation, and IVH Grade 3 were similar between the groups. The incidence of CLD in the abruption group was significantly higher than that of controls (66% versus 43%, p ¼ 0.04). However, there was no significant difference between the groups concerning the incidence of ND and CP. The incidences of chorioamnionitis, funisitis and ischemic changes of the placenta did not differ statistically between the
Extremely premature infant with abruption
DOI: 10.3109/14767058.2014.929109
Table 1. Antenatal and intrapartum characteristics of cases involving abruptions and controls.
Number
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
Maternal age (year) Primipara (%) Gestational age at delivery (weeks) The use of tocolysis MgSO4 (%) Ritodrine hydrochloride (%) Hypertension (%) PROM (%) Intrauterine infection (%) NRFHRs on admission (%) NRFHRs on intrapartum (%) Cesarean delivery (%) Decreased fibrinogen5200 mg/dl (%)
Abruption 32
Control 69
p
29.3 ± 5.8 13 (41) 24.2 ± 1.3
29.9 ± 4.9 22 (32) 24.2 ± 1.2
0.59 0.39 1.0
13 (41) 20 (63) 2 (1) 17 (53) 3 (9) 6 (19) 24 (75) 18 (56) 0
33 (48) 41 (59) 7 (1) 33 (48) 11 (16) 10 (14) 35 (51) 46 (67) 1
0.50 0.77 0.52 0.62 0.37 0.59 0.02 0.31 0.49
Results are expressed as number, incidence (%), or mean ± SD. Comparisons between groups were made using 2 tests. PROM, premature rupture of membranes; NRFHRs, non-reassuring fetal heart rate patterns. Table 2. Neonatal characteristics of infants in abruption and control groups.
Number
Abruption 32
Control 69
p
Boy Birth weight (g) Umbilical artery pH57.1 IUGR (%) Chronic lung disease (%) IVH Grade 3 (%) Intestinal perforation (%) Neonatal death (%) Cerebral palsy (%)
18 (56) 649 ± 143 0 5 (2) 21 (66) 7 (22) 6 (19) 6 (19) 9 (28)
34 (49) 643 ± 125 3 10 (14) 30 (43) 16 (23) 11 (16) 8 (12) 23 (33)
0.51 0.83 0.23 0.88 0.04 0.88 0.73 0.33 0.60
Results are expressed as number, incidence (%), or mean ± SD. Comparisons between groups were made using 2 tests. IUGR, intrauterine growth restriction; IVH, intraventricular hemorrhage. Table 3. Pathological findings of placenta in abruption and control groups.
Number Chorioamnionitis (%) Funisitis (%) Hemosiderin deposition (%) Ischemic changes (%)
Abruption 32 20 7 5 16
(63) (22) (16) (50)
Control 69
p
49 (71) 24 (35) 0 27 (39)
0.39 0.19 50.01 0.30
Results are expressed as number and incidence (%). Comparisons between groups were made using 2 tests.
groups. The incidence of hemosiderin deposition was significantly higher in the abruption group compared to controls (16% versus 0%, p50.01, Table 3).
Discussion Placental abruption with acute inflammation is common at preterm [18]. Histological chorioamnionitis and funisitis were present significantly more often in patients with abruption [19]. We have shown that histological fetal inflammation in extremely premature infants is associated with circulatory disturbances and a risk of IVH ^ 3 [20].
707
It is therefore necessary to consider the effect of inflammation on neonatal outcome in addition to hypoxia due to abruption. Due to co-existing factors, it is difficult to determine which factor is the more deleterious on outcome of an extremely premature infant. However, this study showed no significant differences for the incidence of intrauterine infection, histological chorioamnionitis and funisitis between the abruption and control groups (Table 3). We then simply confirmed the impact of abruption on prognosis among extremely premature infants. Previous reports of neonatal outcome with abruption have been based on near-term to term infants [2,11]. Among the few reports regarding the outcome of extremely premature infants born from a mother with abruption, it was thought that a preterm birth due to abruption is the main determining factor for a poor prognosis [9]. In fact, no difference was found in gestation-specific perinatal mortality in cases of abruption and non-abruption involving infants born less than 28 weeks of gestational age [8]. Perinatal mortality of infants born less than 28 weeks of gestation has currently decreased due to recent perinatal medicine [21,22]. As a consequence, the reduction of neonatal morbidity has become an important issue more than ever. Further efforts will be required to reduce morbidity through detailed studies of the effect of abruption on the outcome of infants born between 22 and 26 weeks of gestation. We showed in this study that NRFHRs developed more easily during labor in the abruption group compared to controls. Furthermore, abruption augmented the incidence of CLD. NRFHRs are frequently seen in the preterm fetus [23]. CLD is commonly observed in extremely premature infants. Nevertheless, abruption increased the neonatal morbidity of extremely premature infants. There is currently debate regarding the efficacy of fetal heart rate monitoring in very preterm fetuses. NRFHRs may occur frequently among preterm deliveries with the most common abnormalities such as VD, late deceleration, and bradycardia [23]. We reported previously that cesarean section in cases of obstetrical indication including NRFHRs is a good practice for extremely premature infants (51000 g) in order to improve neonatal outcome [24]. We have also found that neonates at 23 weeks of gestation receive some benefit regarding NRFHRs from a cesarean section compared with a vaginal birth [25]. Under the present circumstances, we believe that determining fetal status using fetal heart rate monitoring of very preterm fetuses is a useful obstetrical practice. The present study showed that abruption augmented the incidence of intrapartum NRFHRs. When an extremely premature fetus acquires a non-reassuring fetal status regardless of risk factor, it will have a poor prognosis. In the present study, 12 of the 24 NRFHRs (50%) in cases involving abruption resulted in either CP or ND. On the other hand, 15 of the 35 NRFHRs (43%) in controls resulted in either CP or ND. It is important to note that the prognosis was poor in both groups. For cases involving abruption and a more advanced gestational age, a poor neonatal outcome was closely related to the specific FHR pattern, namely, bradycardia [11]. We speculate that preventing any hazardous decelerations could reduce hypoxia and prevent subsequent damage in extremely premature infants. We should keep in mind that it is easy for
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
708
S. Furukawa et al.
the fetal heart rate pattern to deteriorate during labor, where abruption is suspected. As a consequence, cases having a poor prognosis will increase. The present study found that CLD was significantly higher in the abruption group. Interest in the relationship between abruption and neonatal respiratory disease has resulted in studies of the effect of diffuse chorioamniotic hemosiderosis on respiratory diseases [26,27]. Bleeding from intrauterine or retroplacental hemorrhage at an early stage of gestation results in diffuse chorioamniotic hemosiderosis on the placenta, and leads to premature delivery with the combination of IUGR and/or respiratory distress. The incidence of hemosiderin deposition in our study was significantly higher in the abruption group when compared to controls. However, the frequency of hemosiderin deposition (16%) in abruptions was lower than the frequency of CLD (66%). There is wide discrepancy between the incidence of these two factors in cases involving abruption, and we therefore need to consider different factors in our analyses. In contrast, NRFHRs were frequently seen in abruptions, which may lead to more oxygen administration during resuscitation. The findings of our present study highlight the importance for further investigations. The present study has some limitations. First, it involved only one tertiary hospital. We need to validate the incidence of NRFHRs and CLD among different tertiary hospitals. Second, steroid administration did not occur during the study period. Antenatal corticosteroid treatment has been shown to improve neonatal outcome [28]. In the future, the outcomes of neonates should be evaluated by verifying the effect of antenatal corticosteroid treatment on mortality and morbidity such as respiratory disease for extreme prematurity. In conclusion, we demonstrated that abruption increased the incidence of NRFHRs and CLD in infants born between 22 and 26 weeks of gestation. Since the incidence of abruption has increased recently, risk factors should be evaluated to improve neonatal outcome.
Declaration of interest There is no financial or other relationship that might lead to a conflict of interest.
References 1. Ananth CV, Wilcox AJ. Placental abruption and perinatal mortality in the United States. Am J Epidemiol 2001;153:332–37. 2. Ananth CV, Berkowitz GS, Savitz DA, Lapinski RH. Placental abruption and adverse perinatal outcomes. JAMA 1999;282: 1646–51. 3. Matsuda Y, Maeda T, Kouno S. Comparison of neonatal outcome including cerebral palsy between abruptio placentae and placenta previa. Eur J Obstet Gynecol Reprod Biol 2003;106:125–9. 4. Ananth CV, Smulian JC, Demissie K, et al. Placental abruption among singleton and twin births in the United States: risk factor profiles. Am J Epidemiol 2001;153:771–8. 5. Salihu HM, Bekan B, Aliyu MH, et al. Perinatal mortality associated with abruptio placenta in singletons and multiples. Am J Obstet Gynecol 2005;193:198–203. 6. Rasmussen S, Irgens LM, Bergsjo P, Dalaker K. The occurrence of placental abruption in Norway 1967–1991. Acta Obstet Gynecol Scand 1996;75:222–8.
J Matern Fetal Neonatal Med, 2015; 28(6): 705–708
7. Pariente G, Wiznitzer A, Sergienko R, et al. Placental abruption: critical analysis of risk factors and perinatal outcomes. J Matern Fetal Neonatal Med 2011;24:698–702. 8. Ananth CV, VanderWeele TJ. Placental abruption and perinatal mortality with preterm delivery as a mediator: disentangling direct and indirect effects. Am J Epidemiol 2011;174:99–108. 9. Allred LS, Batton D. The effect of placental abruption on the shortterm outcome of premature infants. Am J Perinatol 2004;21: 157–62. 10. Furukawa S, Sameshima H, Ikenoue T, et al. Is the perinatal outcome of placental abruption modified by clinical presentation? J Pregnancy 2011;2011:659615. doi: 10.1155/2011/659615. 11. Takano Y, Furukawa S, Ohashi M, et al. Fetal heart rate patterns related to neonatal brain damage and neonatal death in placental abruption. J Obstet Gynaecol Res 2013;39:61–6. 12. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–22. 13. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:661–6. 14. Kubli FW, Hon EH, Khazin AF, Takemura H. Observations on heart rate and pH in the human fetus during labor. Am J Obstet Gynecol 1969;104:1190–206. 15. Ogawa Y, Iwamura T, Kuriya N, et al. Birth size standards by gestational age for Japanese neonates. Acta Neonatol Japonica 1998;34:624–32 (in Japanese). 16. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529–34. 17. Kai K, Sameshima H, Ikeda T, Ikenoue T. Severe variable deceleration is associated with intestinal perforation in infants born at 22–27 weeks’ gestation. J Matern Fetal Neonatal Med 2009; 22:259–64. 18. Ananth CV, Getahun D, Peltier MR, Smulian JC. Placental abruption in term and preterm gestations: evidence for heterogeneity in clinical pathways. Obstet Gynecol 2006;107:785–92. 19. Darby MJ, Caritis SN, Shen-Schwarz S. Placental abruption in the preterm gestation: an association with chorioamnionitis. Obstet Gynecol 1989;74:88–92. 20. Furukawa S, Sameshima H, Ikenoue T. Circulatory disturbances during the first postnatal 24 hours in extremely premature infants 25 weeks or less of gestation with histological fetal inflammation. J Obstet Gynaecol Res 2008;34:27–33. 21. Ishii N, Kono Y, Yonemoto N, Kusuda S, Fujimura M; Neonatal Research Network, Japan. Outcomes of infants born at 22 and 23 weeks’ gestation. Pediatrics 2013;132:62–71. 22. Kusuda S, Fujimura M, Uchiyama A, Totsu S, Matsunami K; Neonatal Research Network, Japan. Trends in morbidity and mortality among very-low-birth-weight infants from 2003 to 2008 in Japan. Pediatr Res 2012;72:531–8. 23. Ayoubi JM, Audibert F, Vial M, et al. Fetal heart rate and survival of the very premature newborn. Am J Obstet Gynecol 2002;187: 1026–30. 24. Kaneko M, Sameshima H, Kai K, et al. Mortality rates for extremely low-birth weight infants: a regional, population-based study in Japan during 2005–2009. J Obstet Gynaecol Res 2012;38: 1145–51. 25. Furukawa S, Sameshima H, Ikenoue T. The impact of cesarean section on neonatal outcome of infants born at 23 weeks of gestation. Early Hum Dev 2014;90:113–18. 26. Ohyama M, Itani Y, Yamanaka M, et al. Maternal, neonatal, and placental features associated with diffuse chorioamniotic hemosiderosis, with special reference to neonatal morbidity and mortality. Pediatrics 2004;113:800–5. 27. Yoshida S, Kikuchi A, Sunagawa S, et al. Pregnancy complicated by diffuse chorioamniotic hemosiderosis: obstetric features and influence on respiratory diseases of the infant. J Obstet Gynaecol Res 2007;33:788–92. 28. Malloy MH. Antenatal steroid use and neonatal outcome: United States 2007. J Perinatol 2012;32:722–7.
ORIGINAL ARTICLE
The effect of placental abruption on the outcome of extremely premature infants
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
Seishi Furukawa, Koutarou Doi, Ken Furuta, and Hiroshi Sameshima Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Abstract
Keywords
Objective: To determine the effect of placental abruption on the outcome of infants born between 22 and 26 weeks of gestation. Methods: A retrospective study involving 32 cases of placental abruption. Controls were matched to cases according to gestational age and birth weight. Medical records were reviewed to confirm maternal background and neonatal outcome. We compared characteristics of maternal background and neonatal outcome between the two groups. Results: There were no significant differences in the incidence of pregnancy-induced hypertension, low maternal fibrinogen (5200 mg/dl), premature rupture of membrane, intrauterine infection, ischemic changes of the placenta, or funisitis between the groups. Non-reassuring fetal heart rate patterns (NRFHRs) during intrapartum were frequently seen in the placental abruption group compared to controls (75% versus 51%, p ¼ 0.02). However, no differences were found for the incidence of low umbilical artery pH (57.1), cerebral palsy, or neonatal death. The incidence of chronic lung disease (CLD, 66% versus 43%, p ¼ 0.04) and hemosiderin deposition on the placenta (16% versus 0%, p50.01) was higher in abruptions compared to controls. Conclusion: Placental abruption has a risk for the development of NRFHRs and CLD in infants born between 22 and 26 weeks of gestation, but shows no effect on neonatal mortality.
Extremely premature infant, neonatal outcome, placental abruption
Introduction Placental abruption (abruption) is a major cause of poor perinatal outcome [1–3] and occurs in approximately 1% of all pregnancies [4,5]. It is well known that women diagnosed with abruption have a 4- to 6-fold increased risk of a preterm delivery [2]. In fact, the number of abruptions is almost equal in term and preterm births [6], and they are more common in cases involving a lower gestational age [7]. Thus, premature delivery with abruption is an important issue in perinatal care. Ananth et al. showed that gestation-specific perinatal mortality rates were similar between abruption and non-abruption births less than 28 weeks of gestational age [8]. This report suggested that extreme immaturity is a major contributing factor for poor prognosis in cases with a gestational age of less than 28 weeks. Unfortunately, this finding has been given little attention when considering the detailed prognosis of extremely premature infants born in situations involving abruption. However, one report regarding the influence of abruption on neonatal outcome in premature infants around 29 weeks of gestation indicated that a preterm
Address for correspondence: Seishi Furukawa, MD, Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. E-mail: [email protected]
History Received 20 November 2013 Accepted 26 May 2014 Published online 26 June 2014
birth due to abruption is the main determining factor for a poor prognosis [9]. Further studies are definitely needed. We therefore conducted a case–control study to compare the prognosis of infants delivered after abruption between 22 and 26 weeks of gestation with controls of matched gestational age and birth weight without abruption. The current study was conducted in the setting of a tertiary perinatal center with standardized care. We determined the impact of abruption on neonatal outcome of infants born between 22 and 26 weeks of gestation.
Materials and methods This study was conducted retrospectively and there was therefore no need to obtain approval from a suitably constituted Ethics Committee in our institution. We reviewed the medical charts of infants born at 2226 weeks of gestation and admitted to the Perinatal Center, University of Miyazaki, from January 2000 to April 2010. Gestational age was assessed on the basis of the last menstrual period and first-trimester ultrasound fetometry. Our center is the only tertiary perinatal center in the Miyazaki province of Japan. There are 11 000 births per year in the Miyazaki province and our neonatal center deals with over 90% of premature infants with a birth weight of less than 1000 g in our province.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
706
S. Furukawa et al.
We determined abruption by the presence of retro-placental hematoma and clinical presentations (any one or combination of genital bleeding, abdominal pain, pregnancy-induced hypertension (PIH), premature labor, premature rupture of membrane, intrauterine fetal death, or non-reassuring fetal heart rate pattern (NRFHR) [10,11]. Confirmation of retroplacental hematoma was made by visual examination after delivery. Evidence of hematoma immediately after detachment of the placenta was also regarded as a retro-placental hematoma. Cases fulfilling the following criteria were selected: infant living on delivery, a record of FHR on admission and intrapartum, presence of blood gas data for the umbilical artery, and neurodevelopmental assessment performed at an age of 1 year or older. Excluded from the study were cases involving multifetal pregnancy, fetal anomaly, and chromosomal abnormality. A total of 32 infants involving mothers with abruption were thus enrolled in this study. Controls were selected by identifying infants born without abruption within 1 week of the non-control gestational age and a birth weight of 50 g. Each case was matched with at least two controls. A total of 69 controls involving mothers without abruption were enrolled in this study. The following antenatal and intrapartum characteristics were collected: maternal age, parity (primipara), gestational age at birth, use of tocolytics (MgSO4, ritodrine hydrochloride), presence of hypertension, premature rupture of membranes (PROM), intrauterine infection, NRFHRs on admission and intrapartum, cesarean delivery, and decreased maternal fibrinogen (defined as 5200 mg/dl) as an indicator of coagulopathy. In our institution, tocolysis was first conducted with continuous intravenous administration of ritodrine hydrochloride with uterine contractions of four in 20 min or eight in 60 min with progressive changes of dilatation and/or effacement in the cervix. Fetal heart rate monitoring was also conducted to detect potential fetal hypoxia prior to the start of tocolysis. Tocolysis was stopped if fetal asphyxia was evident. If uterine contractions continued, magnesium sulfate was added. Antenatal corticosteroid treatment for mothers with preterm labor was not routinely given at our institution during the study period. In this study, hypertension included chronic hypertension and PIH. Chronic hypertension was defined as hypertension diagnosed prior to conception or within the first 20 weeks of pregnancy. PIH such as gestational hypertension, preeclampsia, eclampsia and superimposed preeclampsia was defined according to the classification of the National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy [12]. Intrauterine infection was defined according to whether the presence of bacteria in amniotic fluid was determined by amniocentesis or clinical chorioamnionitis. Clinical chorioamnionitis was defined as the presence of a maternal febrile condition (438 C), maternal tachycardia (4120 beats/min), maternal leukocytosis (415 000 cells/mm3), and an elevated CRP level (45.0 mg/dl). Fetal heart rate patterns were classified according to the NICHD guideline [13]. Cases of variable decelerations (VDs) were classified into mild, moderate (mVD), and severe (sVD) using Kubli’s classification [14]. In this study, NRFHRs included recurrent late deceleration, recurrent mVD, recurrent sVD, prolonged deceleration, or
J Matern Fetal Neonatal Med, 2015; 28(6): 705–708
bradycardia. The fibrinogen value of the mother was obtained at the day of delivery. The following neonatal characteristics were also collected: sex (boy/girl), birth weight (g), umbilical artery pH (UA pH), intrauterine growth restriction (IUGR), chronic lung disease (CLD), intraventricular hemorrhage (IVH) Grade 3, intestinal perforation, neonatal death (ND), and cerebral palsy (CP). IUGR was defined as a sex-specific birth weight less than the 10th percentile for gestational age according to the Japanese standard growth curve for singletons [15]. Neonatal cranial ultrasound examinations were performed by an attending physician using a 7.5-Hz transducer on admission and then routinely with a repeated examination twice every day until day 7, and weekly up to 1 month. If an attending physician detected IVH, the severity of the IVH was determined by at least two physicians. The grading of IVH follows that described by Papile et al. [16]. Intestinal perforation was diagnosed using clinical characteristics and operative findings [17]. CLD was defined as the need for oxygen supplement at postnatal day 28 or 36 corrected weeks, with positive radiographic findings. Independent pediatric neurologists who were blinded to the study performed the neurodevelopmental assessment of a child with CP. Assessment was performed at an age of 1 year or older. Pathologists in our institution conducted placental histopathological examinations. Gross and histological examination of the placenta and cord were performed, and results were recorded on a standardized form. The following attributes were obtained for each placenta: chorioamnionitis, funisitis, hemosiderin deposition, and ischemic changes. Funisitis was defined when neutrophils were diffusely present throughout the wall of at least one of the umbilical vessels. Ischemic changes included chorangiosis, increased syncytial knots, and atherosis of uteroplacental vessels. Data are expressed as number, incidence (%), or mean ± SD. Comparisons between groups were made using 2 tests. Probability values 50.05 were considered significant.
Results The mean gestational age at delivery in both groups was 24.2 weeks. A comparison of antenatal and intrapartum data between groups showed similarities for maternal age, parity, use of tocolytics, percentage of hypertension, PROM, intrauterine infection, cesarean delivery, and decreased maternal fibrinogen (Table 1). The percentage of NRFHRs on admission was similar between groups (19% versus 14%, p ¼ 0.59). However, the percentage of NRFHRs for intrapartum in the abruption group was significantly higher than that of controls (75% versus 51%, p ¼ 0.02). As shown in Table 2, the incidence of UA pH57.1, IUGR, intestinal perforation, and IVH Grade 3 were similar between the groups. The incidence of CLD in the abruption group was significantly higher than that of controls (66% versus 43%, p ¼ 0.04). However, there was no significant difference between the groups concerning the incidence of ND and CP. The incidences of chorioamnionitis, funisitis and ischemic changes of the placenta did not differ statistically between the
Extremely premature infant with abruption
DOI: 10.3109/14767058.2014.929109
Table 1. Antenatal and intrapartum characteristics of cases involving abruptions and controls.
Number
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
Maternal age (year) Primipara (%) Gestational age at delivery (weeks) The use of tocolysis MgSO4 (%) Ritodrine hydrochloride (%) Hypertension (%) PROM (%) Intrauterine infection (%) NRFHRs on admission (%) NRFHRs on intrapartum (%) Cesarean delivery (%) Decreased fibrinogen5200 mg/dl (%)
Abruption 32
Control 69
p
29.3 ± 5.8 13 (41) 24.2 ± 1.3
29.9 ± 4.9 22 (32) 24.2 ± 1.2
0.59 0.39 1.0
13 (41) 20 (63) 2 (1) 17 (53) 3 (9) 6 (19) 24 (75) 18 (56) 0
33 (48) 41 (59) 7 (1) 33 (48) 11 (16) 10 (14) 35 (51) 46 (67) 1
0.50 0.77 0.52 0.62 0.37 0.59 0.02 0.31 0.49
Results are expressed as number, incidence (%), or mean ± SD. Comparisons between groups were made using 2 tests. PROM, premature rupture of membranes; NRFHRs, non-reassuring fetal heart rate patterns. Table 2. Neonatal characteristics of infants in abruption and control groups.
Number
Abruption 32
Control 69
p
Boy Birth weight (g) Umbilical artery pH57.1 IUGR (%) Chronic lung disease (%) IVH Grade 3 (%) Intestinal perforation (%) Neonatal death (%) Cerebral palsy (%)
18 (56) 649 ± 143 0 5 (2) 21 (66) 7 (22) 6 (19) 6 (19) 9 (28)
34 (49) 643 ± 125 3 10 (14) 30 (43) 16 (23) 11 (16) 8 (12) 23 (33)
0.51 0.83 0.23 0.88 0.04 0.88 0.73 0.33 0.60
Results are expressed as number, incidence (%), or mean ± SD. Comparisons between groups were made using 2 tests. IUGR, intrauterine growth restriction; IVH, intraventricular hemorrhage. Table 3. Pathological findings of placenta in abruption and control groups.
Number Chorioamnionitis (%) Funisitis (%) Hemosiderin deposition (%) Ischemic changes (%)
Abruption 32 20 7 5 16
(63) (22) (16) (50)
Control 69
p
49 (71) 24 (35) 0 27 (39)
0.39 0.19 50.01 0.30
Results are expressed as number and incidence (%). Comparisons between groups were made using 2 tests.
groups. The incidence of hemosiderin deposition was significantly higher in the abruption group compared to controls (16% versus 0%, p50.01, Table 3).
Discussion Placental abruption with acute inflammation is common at preterm [18]. Histological chorioamnionitis and funisitis were present significantly more often in patients with abruption [19]. We have shown that histological fetal inflammation in extremely premature infants is associated with circulatory disturbances and a risk of IVH ^ 3 [20].
707
It is therefore necessary to consider the effect of inflammation on neonatal outcome in addition to hypoxia due to abruption. Due to co-existing factors, it is difficult to determine which factor is the more deleterious on outcome of an extremely premature infant. However, this study showed no significant differences for the incidence of intrauterine infection, histological chorioamnionitis and funisitis between the abruption and control groups (Table 3). We then simply confirmed the impact of abruption on prognosis among extremely premature infants. Previous reports of neonatal outcome with abruption have been based on near-term to term infants [2,11]. Among the few reports regarding the outcome of extremely premature infants born from a mother with abruption, it was thought that a preterm birth due to abruption is the main determining factor for a poor prognosis [9]. In fact, no difference was found in gestation-specific perinatal mortality in cases of abruption and non-abruption involving infants born less than 28 weeks of gestational age [8]. Perinatal mortality of infants born less than 28 weeks of gestation has currently decreased due to recent perinatal medicine [21,22]. As a consequence, the reduction of neonatal morbidity has become an important issue more than ever. Further efforts will be required to reduce morbidity through detailed studies of the effect of abruption on the outcome of infants born between 22 and 26 weeks of gestation. We showed in this study that NRFHRs developed more easily during labor in the abruption group compared to controls. Furthermore, abruption augmented the incidence of CLD. NRFHRs are frequently seen in the preterm fetus [23]. CLD is commonly observed in extremely premature infants. Nevertheless, abruption increased the neonatal morbidity of extremely premature infants. There is currently debate regarding the efficacy of fetal heart rate monitoring in very preterm fetuses. NRFHRs may occur frequently among preterm deliveries with the most common abnormalities such as VD, late deceleration, and bradycardia [23]. We reported previously that cesarean section in cases of obstetrical indication including NRFHRs is a good practice for extremely premature infants (51000 g) in order to improve neonatal outcome [24]. We have also found that neonates at 23 weeks of gestation receive some benefit regarding NRFHRs from a cesarean section compared with a vaginal birth [25]. Under the present circumstances, we believe that determining fetal status using fetal heart rate monitoring of very preterm fetuses is a useful obstetrical practice. The present study showed that abruption augmented the incidence of intrapartum NRFHRs. When an extremely premature fetus acquires a non-reassuring fetal status regardless of risk factor, it will have a poor prognosis. In the present study, 12 of the 24 NRFHRs (50%) in cases involving abruption resulted in either CP or ND. On the other hand, 15 of the 35 NRFHRs (43%) in controls resulted in either CP or ND. It is important to note that the prognosis was poor in both groups. For cases involving abruption and a more advanced gestational age, a poor neonatal outcome was closely related to the specific FHR pattern, namely, bradycardia [11]. We speculate that preventing any hazardous decelerations could reduce hypoxia and prevent subsequent damage in extremely premature infants. We should keep in mind that it is easy for
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/28/15 For personal use only.
708
S. Furukawa et al.
the fetal heart rate pattern to deteriorate during labor, where abruption is suspected. As a consequence, cases having a poor prognosis will increase. The present study found that CLD was significantly higher in the abruption group. Interest in the relationship between abruption and neonatal respiratory disease has resulted in studies of the effect of diffuse chorioamniotic hemosiderosis on respiratory diseases [26,27]. Bleeding from intrauterine or retroplacental hemorrhage at an early stage of gestation results in diffuse chorioamniotic hemosiderosis on the placenta, and leads to premature delivery with the combination of IUGR and/or respiratory distress. The incidence of hemosiderin deposition in our study was significantly higher in the abruption group when compared to controls. However, the frequency of hemosiderin deposition (16%) in abruptions was lower than the frequency of CLD (66%). There is wide discrepancy between the incidence of these two factors in cases involving abruption, and we therefore need to consider different factors in our analyses. In contrast, NRFHRs were frequently seen in abruptions, which may lead to more oxygen administration during resuscitation. The findings of our present study highlight the importance for further investigations. The present study has some limitations. First, it involved only one tertiary hospital. We need to validate the incidence of NRFHRs and CLD among different tertiary hospitals. Second, steroid administration did not occur during the study period. Antenatal corticosteroid treatment has been shown to improve neonatal outcome [28]. In the future, the outcomes of neonates should be evaluated by verifying the effect of antenatal corticosteroid treatment on mortality and morbidity such as respiratory disease for extreme prematurity. In conclusion, we demonstrated that abruption increased the incidence of NRFHRs and CLD in infants born between 22 and 26 weeks of gestation. Since the incidence of abruption has increased recently, risk factors should be evaluated to improve neonatal outcome.
Declaration of interest There is no financial or other relationship that might lead to a conflict of interest.
References 1. Ananth CV, Wilcox AJ. Placental abruption and perinatal mortality in the United States. Am J Epidemiol 2001;153:332–37. 2. Ananth CV, Berkowitz GS, Savitz DA, Lapinski RH. Placental abruption and adverse perinatal outcomes. JAMA 1999;282: 1646–51. 3. Matsuda Y, Maeda T, Kouno S. Comparison of neonatal outcome including cerebral palsy between abruptio placentae and placenta previa. Eur J Obstet Gynecol Reprod Biol 2003;106:125–9. 4. Ananth CV, Smulian JC, Demissie K, et al. Placental abruption among singleton and twin births in the United States: risk factor profiles. Am J Epidemiol 2001;153:771–8. 5. Salihu HM, Bekan B, Aliyu MH, et al. Perinatal mortality associated with abruptio placenta in singletons and multiples. Am J Obstet Gynecol 2005;193:198–203. 6. Rasmussen S, Irgens LM, Bergsjo P, Dalaker K. The occurrence of placental abruption in Norway 1967–1991. Acta Obstet Gynecol Scand 1996;75:222–8.
J Matern Fetal Neonatal Med, 2015; 28(6): 705–708
7. Pariente G, Wiznitzer A, Sergienko R, et al. Placental abruption: critical analysis of risk factors and perinatal outcomes. J Matern Fetal Neonatal Med 2011;24:698–702. 8. Ananth CV, VanderWeele TJ. Placental abruption and perinatal mortality with preterm delivery as a mediator: disentangling direct and indirect effects. Am J Epidemiol 2011;174:99–108. 9. Allred LS, Batton D. The effect of placental abruption on the shortterm outcome of premature infants. Am J Perinatol 2004;21: 157–62. 10. Furukawa S, Sameshima H, Ikenoue T, et al. Is the perinatal outcome of placental abruption modified by clinical presentation? J Pregnancy 2011;2011:659615. doi: 10.1155/2011/659615. 11. Takano Y, Furukawa S, Ohashi M, et al. Fetal heart rate patterns related to neonatal brain damage and neonatal death in placental abruption. J Obstet Gynaecol Res 2013;39:61–6. 12. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–22. 13. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:661–6. 14. Kubli FW, Hon EH, Khazin AF, Takemura H. Observations on heart rate and pH in the human fetus during labor. Am J Obstet Gynecol 1969;104:1190–206. 15. Ogawa Y, Iwamura T, Kuriya N, et al. Birth size standards by gestational age for Japanese neonates. Acta Neonatol Japonica 1998;34:624–32 (in Japanese). 16. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529–34. 17. Kai K, Sameshima H, Ikeda T, Ikenoue T. Severe variable deceleration is associated with intestinal perforation in infants born at 22–27 weeks’ gestation. J Matern Fetal Neonatal Med 2009; 22:259–64. 18. Ananth CV, Getahun D, Peltier MR, Smulian JC. Placental abruption in term and preterm gestations: evidence for heterogeneity in clinical pathways. Obstet Gynecol 2006;107:785–92. 19. Darby MJ, Caritis SN, Shen-Schwarz S. Placental abruption in the preterm gestation: an association with chorioamnionitis. Obstet Gynecol 1989;74:88–92. 20. Furukawa S, Sameshima H, Ikenoue T. Circulatory disturbances during the first postnatal 24 hours in extremely premature infants 25 weeks or less of gestation with histological fetal inflammation. J Obstet Gynaecol Res 2008;34:27–33. 21. Ishii N, Kono Y, Yonemoto N, Kusuda S, Fujimura M; Neonatal Research Network, Japan. Outcomes of infants born at 22 and 23 weeks’ gestation. Pediatrics 2013;132:62–71. 22. Kusuda S, Fujimura M, Uchiyama A, Totsu S, Matsunami K; Neonatal Research Network, Japan. Trends in morbidity and mortality among very-low-birth-weight infants from 2003 to 2008 in Japan. Pediatr Res 2012;72:531–8. 23. Ayoubi JM, Audibert F, Vial M, et al. Fetal heart rate and survival of the very premature newborn. Am J Obstet Gynecol 2002;187: 1026–30. 24. Kaneko M, Sameshima H, Kai K, et al. Mortality rates for extremely low-birth weight infants: a regional, population-based study in Japan during 2005–2009. J Obstet Gynaecol Res 2012;38: 1145–51. 25. Furukawa S, Sameshima H, Ikenoue T. The impact of cesarean section on neonatal outcome of infants born at 23 weeks of gestation. Early Hum Dev 2014;90:113–18. 26. Ohyama M, Itani Y, Yamanaka M, et al. Maternal, neonatal, and placental features associated with diffuse chorioamniotic hemosiderosis, with special reference to neonatal morbidity and mortality. Pediatrics 2004;113:800–5. 27. Yoshida S, Kikuchi A, Sunagawa S, et al. Pregnancy complicated by diffuse chorioamniotic hemosiderosis: obstetric features and influence on respiratory diseases of the infant. J Obstet Gynaecol Res 2007;33:788–92. 28. Malloy MH. Antenatal steroid use and neonatal outcome: United States 2007. J Perinatol 2012;32:722–7.
