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Reduced fetal movements is twin pregnancies and the association with adverse neonatal outcomes
European Journal of Obstetrics & Gynecology and Reproductive Biology 246 (2020) 165–168
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Full length article
Reduced fetal movements is twin pregnancies and the association with adverse neonatal outcomes Michal Levy* , Michal Kovo, Yakira Izaik, Emilie Ben-Ezry, Noa Gonen, Giulia Barda, Jacob Bar, Eran Weiner Departments of Obstetrics & Gynecology, the Edith Wolfson Medical Center, Holon, Israel1
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 November 2019 Received in revised form 24 January 2020 Accepted 31 January 2020 Available online xxx
Objective: Reduced fetal movements (RFM) is an obstetric complaint known to be associated with adverse neonatal outcomes and should serve as an alarming sign in obstetric triage. Whether this assumption holds for twin pregnancies, is still an obstetric enigma, and this complaint is sometimes overlooked in twins. We, therefore, aimed to study neonatal outcomes in twin pregnancies complicated by RFM. We hypothesised that in twin pregnancy, maternal ability to perceive RFM will be limited, and therefore, will not be associated with adverse neonatal outcome. Study design: Included were all dichorionic twin pregnancies between 2009–2019 who presented to our obstetric triage at a gestational age >34 weeks with an isolated complaint of RFM and delivered during the subsequent two weeks (RFM group). The control group included patients with twin pregnancies (matched for gestational age and maternal age) who presented for routine assessment and reported regular fetal movements throughout pregnancy (no RFM group). Data regarding pregnancy, delivery, and neonatal outcomes were compared between the groups. The primary outcome was a composite of adverse neonatal outcomes, which included one or more of the following: neonatal hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death. Multivariable regression analysis was used to identify independent associations with adverse neonatal outcomes. Results: Maternal demographics and gestational age at delivery did not differ between the RFM group (n = 83 pregnancies and 166 neonates) and the no RFM group (n = 83 pregnancies and 166 neonates). Neonatal birthweights, as well as the rate of birthweights <10th centile, did not differ between the groups. There were 2 cases of fetal demise diagnosed at triage in the RFM group. The rate of the primary outcome, as well as NICU admissions, were significantly higher in the RFM group compared to the no RFM group (29.5 % vs. 19.2 %, p = 0.01 and 32.5 % vs. 19.2 %, p = 0.001). In multivariable analysis RFM (aOR = 1.18, 95 % CI = 1.06–2.73), and GA at delivery (aOR = 0.88, 95 % CI = 0.67-0.97) were associated with adverse neonatal outcome-independent from background confounders. Conclusion: Patients presented to obstetric triage with twin pregnancies and isolated RFM had higher rates of adverse neonatal outcomes and NICU admissions compared to twin pregnancies without RFM. © 2020 Elsevier B.V. All rights reserved.
Keywords: Twins Pregnancy Dichorionic Reduced fetal movements Neonatal outcome
Introduction Fetal movement counting is a method by which a pregnant woman quantifies the movements she feels to assess fetal wellbeing. Maternal assessment of fetal movements is a simple method for monitoring fetal wellbeing that does not require
* Corresponding author at: Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, P.O. Box 5, Holon, 58100, Israel. E-mail address: [email protected] (M. Levy). 1 Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. https://doi.org/10.1016/j.ejogrb.2020.01.050 0301-2115/© 2020 Elsevier B.V. All rights reserved.
clinician involvement or any specific equipment [1]. The purpose is to try to reduce perinatal morbidity and mortality by alerting caregivers of possible fetal compromise or distress. Reduced fetal movements (RFM) has been demonstrated in numerous studies to be associated with adverse pregnancy outcomes including fetal growth restriction (FGR) and stillbirth [2–5]. There are numerous techniques for charting fetal movement. The Cardiff 'count-to-10' method has been studied since 1984 [6]. Smith et al. compared three different methods of fetal movement counting and suggested that the’ count-to-10’ method is more user-friendly than the other methods [7]. Christensen et al. and Gomez et al. also found higher rates of compliance with the’ count-to-10’ method
166
M. Levy et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 246 (2020) 165–168
[8,9]. Another technique is the ‘Sadovsky technique’, in short, in the Sadovsky method, a woman counts fetal movements three times a day after meals [10]. Currently, no consensus exists about what constitutes normal fetal movements in late pregnancy. Still, according to all methods mentioned, two hours of no fetal movements are an indication for fetal assessment. The patterns of fetal movements in twin pregnancies were previously studied. Few studies have suggested that twins compared with singletons are more active [11,12]. Several authors have reported a high degree of synchrony within twin pairs regarding body movements [13,14]. Gallagher et al. found that twins exhibited synchronous behaviour patterns (basically sleep or awake state) 94.7 % of the time [14]. In contrast, Zimmer et al. found the overall synchronous fetal activity rate was only 53.3 % [15]. They also concluded fetal sex or presentation had no significant effect on fetal activity in twin pregnancies. In singleton pregnancies, an acute reduction in fetal movements is an indication for an immediate assessment of fetal wellbeing [16–18]. Whether this assumption holds for twins is an issue of controversy among obstetricians, and this complaint is sometimes overlooked. We, therefore, aimed to study neonatal outcomes in twin pregnancies complicated by RFM. Our hypothesis was that in twin pregnancy, RFM is a limited predictor of adverse neonatal outcome due to maternal difficulty to monitor fetal movements.
gestations with known neonatal chromosomal or structural anomalies, gestations of higher-order multiple pregnancies, and cases in which there were missing data (cases that deliver in a different institution). In all participants, the gestational age and chorionicity were confirmed by first-trimester ultrasonography. Our departmental protocol for routine fetal assessment, also implies for RFM and include a nonstress test for at least 20 min and ultrasonographic examination including biophysical profile, amniotic fluid volume, and an estimation of fetal weight. Doppler studies were performed in SGA fetuses. If the patient regained normal fetal movements while in triage, she would discharge and instructed to repeat fetal well-being assessment with her primary obstetrician in the following 2–3 days. A patient who still reported RFM after the above triage workup was hospitalized for further evaluation For the study, maternal demographics, pregnancy, and neonatal outcomes were compared between twins pregnancy with RFM (RFM group) and twins pregnancy without RFM (no RFM group). The primary outcome was a composite of adverse neonatal outcomes, which included one or more of the following: neonatal hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death.
Materials and methods
The following data were collected from the patients’s medical and surgical files of their pregnancy: age, gestational age at delivery, parity, assisted reproduction technology (ART), prepregnancy BMI, smoking, thrombophilia (defined as any thrombophilia, inherited or acquired, which necessitated thromboprophylaxis according to the practice bulletins of the American College of Obstetricians and Gynecologists [20,21]), preeclampsia with or without severe features (preeclampsia was diagnosed according to American College of Obstetricians and Gynecologists criteria) [22], pre-gestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM), Cesarean delivery rates and Cesarean delivery for non-reassuring fetal heart rate (NRFHR). Immediately after birth, all neonates were examined by pediatricians. The birthweight percentile for gestational age was assigned using the updated local growth charts [23]. The following data were collected from the neonatal charts : birthweight, fetal demise, Apgar scores, cord blood Ph, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia (defined as basal glucose <40 mg/dL), respiratory morbidity defined as one of the following - respiratory distress syndrome, or mechanical ventilation, or need for respiratory support, cerebral morbidity defined as one of the following - intraventricular hemorrhage (all grades), seizures or hypoxic-ischemic encephalopathy, sepsis (positive blood or cerebrospinal fluid
This is retrospective cohort study. The medical records of all dichorionic twin pregnancies between 2009–2019 who presented to our obstetric triage in a single university-affiliated medical center were reviewed. Included in the study, only patients presenting at a gestational age >34 weeks with an isolated complaint of RFM and delivered during the subsequent two weeks (RFM group). The control group included patients with dichorionic twin pregnancies (matched for gestational age and maternal age) who presented for routine assessment and reported regular fetal movements throughout pregnancy (twins no RFM group). The matched control pregnancy was defined as the next available twin delivery from our delivery logbook, who met all matching criteria. RFM was retrospectively defined as a subjective maternal perception of RFM for at least 12 h [19]. Only participants with RFM who delivered within two weeks from their presentation to obstetric triage were included in the study. This two-week limit was empirically decided by us to allow a temporal association between RFM and pregnancy and neonatal outcomes. Excluded from the study were pregnancies delivered > two weeks from their referral for RFM, monochorionic twins,
Data collection
Table 1 Maternal demographics of the study groups. p-value
Twins no RFM n = 83
Twins with RFM n = 83
0.89 0.95 0.75 0.27 0.95 0.45 1.0 0.71 0.79 0.51 1.0
31.3 6.1 36.4 1.5 35 (42.1) 47 (56.6) 25.4 5.5 7 (8.4) 0 (0) 3 (3.6) 9 (10.8) 56 (67.4) 5 (6.0)
30.4 4.8 36.5 0.9 32 (38.5) 39 (46.9) 25.9 7.8 11 (13.2) 1 (1.2) 5 (6.0) 7 (8.4) 51 (61.4) 6 (7.2)
Maternal age (years) Gestational age at delivery (weeks) Nulliparity ART Pre-pregnancy BMI (kg/m [2]) Smoking Thrombophilia Preeclampsia mild or severe (%) Any DM (%) Cesarean delivery Cesarean delivery for NRFHR
Continuous variables are presented as mean SD and categorical variables as n (%). BMI- body mass index; ART – assisted reproduction technology (ovulation induction or in-vitro fertilization); DM – diabetes mellitus; NRFHR – non reassuring fetal heart rate.
M. Levy et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 246 (2020) 165–168
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Table 2 Neonatal outcomes of the study groups.
Neonatal weight (grams) SGA 10th percentile Fetal demise 5-minute Apgar score 7 Umbilical cord pH 7.1 NICU admission Neonatal hypoglycemia Respiratory morbidity * Cerebral morbidity ** Neonatal sepsis Phototherapy Blood transfusions Necrotizing enterocolitis Neonatal death Composite adverse neonatal outcome
Twins with RFM n = 166
Twins no RFM n = 166
p-value
2342.5 433.6 15 (9.03) 2 (1.2) 6 (3.6) 14 (8.43) 54 (32.5) 11 (6.6) 22 (13.2) 10 (6.0) 2 (1.2) 25 (15.0) 1 (0.6) 0 (0) 3 (1.8) 49 (29.5)
2603.2 382.5 9 (5.4) 0 (0) 1 (0.6) 10 (6.0) 32 (19.2) 10 (6.0) 16 (9.6) 2 (1.2) 0 (0) 11 (6.6) 0 (0) 0 (0) 0 (0) 32 (19.2)
0.65 0.27 0.49 0.11 0.50 0.001 1.0 0.35 0.03 0.49 0.01 1.0 1.0 0.24 0.01
Continuous variables are presented as mean SD and categorical variables as n (%) NICU- neonatal intensive care unit. *Respiratory morbidity- respiratory distress syndrome, or mechanical ventilation, or need for respiratory support. **Cerebral morbidity -intra-ventricular hemorrhage (all grades), or seizures or hypoxic-ischemic encephalopathy. Values in bold are statistically significant. Composite adverse neonatal outcome – one or more of the following: hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death.
culture), phototherapy, blood transfusion, necrotizing enterocolitis (NEC), and neonatal death (death in the first 28 days of life). Statistical analysis Data were analyzed with Epi Info, version 7.0 (Centers for Disease Control and Prevention, Atlanta, GA). Continuous variables were calculated as mean standard deviation (SD) and compared using the Student’s t-test or the non-parametric Mann-Whitney test as appropriate. Categorical variables were calculated as a rate (percentage) and compared with Chi square or Fisher’s exact test as appropriate. All tests were two tailed, and the threshold for statistical significance was defined as p-value < 0.05. A multivariable regression analysis was performed to identify independent associations with adverse neonatal outcome. In this analysis composite adverse neonatal outcome served as the dependent variable while maternal age, RFM, GA at delivery, smoking, preeclampsia, DM, BMI, and SGA served as independent variables. Ethical approval was obtained from local Research Ethics Committees (0022-19-WOMC) Results The final groups consisted of 83 twin pregnancy (166 neonates) with RFM complaint in the two weeks prior delivery; all referred >34 weeks of gestation. The control group consisted of 83 twin pregnancy (166 neonates), without RFM during pregnancy, matched for maternal age and gestational age. Two neonates from the RFM group, included in the analyses, were demised at presentation. Maternal and delivery characteristics are summarized in Table 1. There were no statistically significant differences in maternal and delivery characteristics. Neonatal outcome of the study groups presented in Table 2. Neonatal birthweights, as well as the rate of birthweights <10th centile, did not differ between the groups. The rate of the primary outcome was significantly higher in the RFM group compared to the no RFM group (29.5 % vs. 19.2 %, p = 0.01). The rate of NICU admissions, cerebral morbidity, and the need for phototherapy were also significantly higher in the RFM group compared to the no RFM group (32.5 % vs. 19.2 %, p = 0.001, 6.0 % vs. 1.2 %, p = 0.03 and 15.0 % vs. 6.6 %, p = 0.01 respectively).
The results of multivariable regression analysis to identify independent associations with the adverse neonatal outcome are presented in Table 3. RFM (aOR = 1.18, 95 % CI = 1.06–2.73), and GA at delivery (aOR = 0.88, 95 % CI = 0.67–0.97) were associated with adverse neonatal outcome - independent from background confounders. Discussion To our knowledge, this is the first study that compares delivery and neonatal outcomes in twin pregnancies with and without RFM. We found a higher rate of adverse neonatal outcome, as well as NICU admissions in the RFM group, compared to the no RFM group. These findings were associated with RFM independent of all background confounders. A reduction in fetal movement may be physiological, such as during fetal sleep states, and it may also result from maternal subjective difficulty in appreciating the fetal activity, especially in twin pregnancies. However, it may be a sign of impending or existing pathology, and fetal compromise. Previous studies, in singleton pregnancies, published that up to 87 % of fetal movements are accurately perceived simultaneously by the mother when recorded using an external electromagnetic device [18,24] no comparable studies were published regarding twins. Previous studies aimed to determine the diagnostic value of fetal movements counting by the mother; some investigated the required mean time for counting fetal movements in different methods - all studies were performed on singleton pregnancies. Few studies found that fetal movement counting tests can be used as primary screening methods in predicting fetal distress, increased identification of fetal
Table 3 Results of a multivariable regression analysis for independent associations with adverse neonatal outcome. Variable
aOR
95 % CI
Maternal age Gestational age at delivery Reduced fetal movements Smoking Body mass index Preeclampsia Diabetes Mellitus Small for gestational age (SGA)
1.32 0.88 1.18 1.12 1.05 1.23 1.08 1.09
0.65-2.96 0.67-0.97 1.06-2.73 0.88-2.69 0.77-3.36 0.88-3.14 0.67-2.57 0.89-3.66
Values in bold are statistically significant.
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growth restriction, and improved perinatal outcome [25,26]. Berbey et al. studied 752 pregnancies with a gestational age of more than 35 weeks; they found that decreased fetal movements reported by the mother were significantly predictive for the abnormal results of fetal heart rate monitor or biophysical score on ultrasound and adverse pregnancy outcomes [27]. Nevertheless, some studies could not find an association between RFM and adverse neonatal outcomes. According to Harrington et al. patients, who present solely with RFM in the third trimester, without any other risk factor, do not appear to constitute a high-risk group; their pregnancy outcome is as good as that of the general population [28]. Although the numbers in this study are relatively small, their results support the Cochrane’s findings [29]. Importantly all these data are derived from singleton pregnancies, and data regarding twins are sparse. The evidence from our study indicates that a complaint of RFM during a dichorionic twin pregnancy, beyond 34 weeks of gestation, might be associated with a less favorable neonatal outcome. Consequently, these patients require further fetal assessment and tests to identify a possible fetal compromise/distress. Several strengths should be noted in the current study. First, according to our knowledge, this is the first attempt to study the association between RFM in twin pregnancies and adverse neonatal outcomes. Second, we were able to assess a relatively large cohort of 83 pregnancies and 166 neonates in each group. Third, we were able to demonstrate the association between RFM in twins and adverse neonatal outcomes independent of background confounders. Lastly, the study was performed under the circumstances of a general obstetric triage, which is probably similar in many birthing units. This strengthens the generalizability of our results. The current study is not without limitations. First, we are aware that RFM was a subjective impression of the patient, which is not well defined or standardized. Second, we have only collected short term neonatal outcomes. RFM might suggest a profound neurological or skeletal disorder. Lastly, the use of a composite outcome may be viewed as a limitation of this study. A direct biological linkage between each of the components of the composite and RFM is difficult to describe. However, we believe the use of a composite was necessary because the individual components of the composite are rare complications. We have described and validated the same composite neonatal outcomes in our previous publications with other pregnancy complications [30,31]. In conclusion, in contrast to our hypothesis, RFM in twins was independently associated with adverse neonatal outcomes. These findings may suggest that though commonly overlooked in twin pregnancies, RFM still should be considered as an "alert sign" in every obstetric triage. Future prospective studies are needed to establish the value of fetal movements counting in twin pregnancies and its ability to predict adverse neonatal outcome. Sources of financial support None Declaration of Competing Interest None. References [1] Mangesi L, Hofmeyr GJ, Smith V, Smyth RMD. Fetal movement counting for assessment of fetal wellbeing. Cochrane Database Syst Rev 2015(October (10)) CD004909. [2] Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births defined by customised versus population-based birthweight standards. BJOG 2001;108(August (8)):830–4.
[3] Froen JF, Gardosi JO, Thurmann A, Francis A, Stray-Pedersen B. Restricted fetal growth in sudden intrauterine unexplained death. Acta Obstet Gynecol Scand 2004;83(September (9)):801–7. [4] Gilbert WM, Danielsen B. Pregnancy outcomes associated with intrauterine growth restriction. Am J Obstet Gynecol 2003;188(June (6)):1596–601. [5] Lindqvist PG, Molin J. Does antenatal identification of small-for-gestational age fetuses significantly improve their outcome? Ultrasound Obstet Gynecol 2005;25(March (3)):258–64. [6] Grant A, Hepburn M. Merits of an individualized approach to fetal movement counting compared with fixed-time and fixed-number methods. Br J Obstet Gynaecol 1984;91(11):1087–90. [7] Smith CV, Davis SA, Rayburn WF. Patients’ acceptance of monitoring fetal movement. A randomized comparison of charting techniques. J Reprod Med 1992;37(February (2)):144–6. [8] Christensen FC, Olson K, Rayburn WF. Cross-over trial comparing maternal acceptance of two fetal movement charts. J Matern Neonatal Med [Internet] 2003;14(2)118–22, doi:http://dx.doi.org/10.1080/jmf.14.2.118.122 Jan 1 Available from:. [9] Gomez LM, De la Vega G, Padilla L, Bautista F, Villar A. Compliance with a fetal movement chart by high-risk obstetric patients in a Peruvian hospital. Am J Perinatol 2007;24(February (2)):89–93. [10] Sadovsky E, Ohel G, Simon A, Aboulafia Y. Decreased fetal activity in complications of pregnancy. Int J Gynaecol Obstet 1986;24(December (6)):443–6. [11] Sadovsky E, Ohel G, Simon A. Ultrasonographical evaluation of the incidence of simultaneous and independent movements in twin fetuses. Gynecol Obstet Invest 1987;23(1):5–9. [12] Sadovsky E, Samueloff A, Sadovsky Y, Ohel G. Incidence of spontaneous and evoked fetal movements. Gynecol Obstet Invest [Internet] 1986;21(4)177–81, doi:http://dx.doi.org/10.1159/000298950 Available from:. [13] Piontelli A, Bocconi L, Kustermann A, Tassis B, Zoppini C, Nicolini U. 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The cochrane databases of randomized controlled trials and systematic reviews in pregnancy, childbirth and neonatal care. Semin Neonatol [Internet] 1997;2(3)211–9. . Available from: http://www. sciencedirect.com/science/article/pii/S1084275697800176. [30] Levy M, Kovo M, Schreiber L, Kleiner I, Grinstein E, Koren L, et al. Pregnancy outcomes in correlation with placental histopathology in subsequent pregnancies complicated by fetal growth restriction. Placenta [Internet] 2019;80(March)36–41. . Available from: https://linkinghub.elsevier.com/ retrieve/pii/S0143400419300736. [31] Kovo M, Schreiber L, Ben-Haroush A, Cohen G, Weiner E, Golan A, et al. The placental factor in early- and late-onset normotensive fetal growth restriction. Placenta [Internet] 2013;34(4)320–4, doi:http://dx.doi.org/10.1016/j.placenta.2012.11.010 Available from:.
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Full length article
Reduced fetal movements is twin pregnancies and the association with adverse neonatal outcomes Michal Levy* , Michal Kovo, Yakira Izaik, Emilie Ben-Ezry, Noa Gonen, Giulia Barda, Jacob Bar, Eran Weiner Departments of Obstetrics & Gynecology, the Edith Wolfson Medical Center, Holon, Israel1
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 November 2019 Received in revised form 24 January 2020 Accepted 31 January 2020 Available online xxx
Objective: Reduced fetal movements (RFM) is an obstetric complaint known to be associated with adverse neonatal outcomes and should serve as an alarming sign in obstetric triage. Whether this assumption holds for twin pregnancies, is still an obstetric enigma, and this complaint is sometimes overlooked in twins. We, therefore, aimed to study neonatal outcomes in twin pregnancies complicated by RFM. We hypothesised that in twin pregnancy, maternal ability to perceive RFM will be limited, and therefore, will not be associated with adverse neonatal outcome. Study design: Included were all dichorionic twin pregnancies between 2009–2019 who presented to our obstetric triage at a gestational age >34 weeks with an isolated complaint of RFM and delivered during the subsequent two weeks (RFM group). The control group included patients with twin pregnancies (matched for gestational age and maternal age) who presented for routine assessment and reported regular fetal movements throughout pregnancy (no RFM group). Data regarding pregnancy, delivery, and neonatal outcomes were compared between the groups. The primary outcome was a composite of adverse neonatal outcomes, which included one or more of the following: neonatal hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death. Multivariable regression analysis was used to identify independent associations with adverse neonatal outcomes. Results: Maternal demographics and gestational age at delivery did not differ between the RFM group (n = 83 pregnancies and 166 neonates) and the no RFM group (n = 83 pregnancies and 166 neonates). Neonatal birthweights, as well as the rate of birthweights <10th centile, did not differ between the groups. There were 2 cases of fetal demise diagnosed at triage in the RFM group. The rate of the primary outcome, as well as NICU admissions, were significantly higher in the RFM group compared to the no RFM group (29.5 % vs. 19.2 %, p = 0.01 and 32.5 % vs. 19.2 %, p = 0.001). In multivariable analysis RFM (aOR = 1.18, 95 % CI = 1.06–2.73), and GA at delivery (aOR = 0.88, 95 % CI = 0.67-0.97) were associated with adverse neonatal outcome-independent from background confounders. Conclusion: Patients presented to obstetric triage with twin pregnancies and isolated RFM had higher rates of adverse neonatal outcomes and NICU admissions compared to twin pregnancies without RFM. © 2020 Elsevier B.V. All rights reserved.
Keywords: Twins Pregnancy Dichorionic Reduced fetal movements Neonatal outcome
Introduction Fetal movement counting is a method by which a pregnant woman quantifies the movements she feels to assess fetal wellbeing. Maternal assessment of fetal movements is a simple method for monitoring fetal wellbeing that does not require
* Corresponding author at: Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, P.O. Box 5, Holon, 58100, Israel. E-mail address: [email protected] (M. Levy). 1 Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. https://doi.org/10.1016/j.ejogrb.2020.01.050 0301-2115/© 2020 Elsevier B.V. All rights reserved.
clinician involvement or any specific equipment [1]. The purpose is to try to reduce perinatal morbidity and mortality by alerting caregivers of possible fetal compromise or distress. Reduced fetal movements (RFM) has been demonstrated in numerous studies to be associated with adverse pregnancy outcomes including fetal growth restriction (FGR) and stillbirth [2–5]. There are numerous techniques for charting fetal movement. The Cardiff 'count-to-10' method has been studied since 1984 [6]. Smith et al. compared three different methods of fetal movement counting and suggested that the’ count-to-10’ method is more user-friendly than the other methods [7]. Christensen et al. and Gomez et al. also found higher rates of compliance with the’ count-to-10’ method
166
M. Levy et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 246 (2020) 165–168
[8,9]. Another technique is the ‘Sadovsky technique’, in short, in the Sadovsky method, a woman counts fetal movements three times a day after meals [10]. Currently, no consensus exists about what constitutes normal fetal movements in late pregnancy. Still, according to all methods mentioned, two hours of no fetal movements are an indication for fetal assessment. The patterns of fetal movements in twin pregnancies were previously studied. Few studies have suggested that twins compared with singletons are more active [11,12]. Several authors have reported a high degree of synchrony within twin pairs regarding body movements [13,14]. Gallagher et al. found that twins exhibited synchronous behaviour patterns (basically sleep or awake state) 94.7 % of the time [14]. In contrast, Zimmer et al. found the overall synchronous fetal activity rate was only 53.3 % [15]. They also concluded fetal sex or presentation had no significant effect on fetal activity in twin pregnancies. In singleton pregnancies, an acute reduction in fetal movements is an indication for an immediate assessment of fetal wellbeing [16–18]. Whether this assumption holds for twins is an issue of controversy among obstetricians, and this complaint is sometimes overlooked. We, therefore, aimed to study neonatal outcomes in twin pregnancies complicated by RFM. Our hypothesis was that in twin pregnancy, RFM is a limited predictor of adverse neonatal outcome due to maternal difficulty to monitor fetal movements.
gestations with known neonatal chromosomal or structural anomalies, gestations of higher-order multiple pregnancies, and cases in which there were missing data (cases that deliver in a different institution). In all participants, the gestational age and chorionicity were confirmed by first-trimester ultrasonography. Our departmental protocol for routine fetal assessment, also implies for RFM and include a nonstress test for at least 20 min and ultrasonographic examination including biophysical profile, amniotic fluid volume, and an estimation of fetal weight. Doppler studies were performed in SGA fetuses. If the patient regained normal fetal movements while in triage, she would discharge and instructed to repeat fetal well-being assessment with her primary obstetrician in the following 2–3 days. A patient who still reported RFM after the above triage workup was hospitalized for further evaluation For the study, maternal demographics, pregnancy, and neonatal outcomes were compared between twins pregnancy with RFM (RFM group) and twins pregnancy without RFM (no RFM group). The primary outcome was a composite of adverse neonatal outcomes, which included one or more of the following: neonatal hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death.
Materials and methods
The following data were collected from the patients’s medical and surgical files of their pregnancy: age, gestational age at delivery, parity, assisted reproduction technology (ART), prepregnancy BMI, smoking, thrombophilia (defined as any thrombophilia, inherited or acquired, which necessitated thromboprophylaxis according to the practice bulletins of the American College of Obstetricians and Gynecologists [20,21]), preeclampsia with or without severe features (preeclampsia was diagnosed according to American College of Obstetricians and Gynecologists criteria) [22], pre-gestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM), Cesarean delivery rates and Cesarean delivery for non-reassuring fetal heart rate (NRFHR). Immediately after birth, all neonates were examined by pediatricians. The birthweight percentile for gestational age was assigned using the updated local growth charts [23]. The following data were collected from the neonatal charts : birthweight, fetal demise, Apgar scores, cord blood Ph, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia (defined as basal glucose <40 mg/dL), respiratory morbidity defined as one of the following - respiratory distress syndrome, or mechanical ventilation, or need for respiratory support, cerebral morbidity defined as one of the following - intraventricular hemorrhage (all grades), seizures or hypoxic-ischemic encephalopathy, sepsis (positive blood or cerebrospinal fluid
This is retrospective cohort study. The medical records of all dichorionic twin pregnancies between 2009–2019 who presented to our obstetric triage in a single university-affiliated medical center were reviewed. Included in the study, only patients presenting at a gestational age >34 weeks with an isolated complaint of RFM and delivered during the subsequent two weeks (RFM group). The control group included patients with dichorionic twin pregnancies (matched for gestational age and maternal age) who presented for routine assessment and reported regular fetal movements throughout pregnancy (twins no RFM group). The matched control pregnancy was defined as the next available twin delivery from our delivery logbook, who met all matching criteria. RFM was retrospectively defined as a subjective maternal perception of RFM for at least 12 h [19]. Only participants with RFM who delivered within two weeks from their presentation to obstetric triage were included in the study. This two-week limit was empirically decided by us to allow a temporal association between RFM and pregnancy and neonatal outcomes. Excluded from the study were pregnancies delivered > two weeks from their referral for RFM, monochorionic twins,
Data collection
Table 1 Maternal demographics of the study groups. p-value
Twins no RFM n = 83
Twins with RFM n = 83
0.89 0.95 0.75 0.27 0.95 0.45 1.0 0.71 0.79 0.51 1.0
31.3 6.1 36.4 1.5 35 (42.1) 47 (56.6) 25.4 5.5 7 (8.4) 0 (0) 3 (3.6) 9 (10.8) 56 (67.4) 5 (6.0)
30.4 4.8 36.5 0.9 32 (38.5) 39 (46.9) 25.9 7.8 11 (13.2) 1 (1.2) 5 (6.0) 7 (8.4) 51 (61.4) 6 (7.2)
Maternal age (years) Gestational age at delivery (weeks) Nulliparity ART Pre-pregnancy BMI (kg/m [2]) Smoking Thrombophilia Preeclampsia mild or severe (%) Any DM (%) Cesarean delivery Cesarean delivery for NRFHR
Continuous variables are presented as mean SD and categorical variables as n (%). BMI- body mass index; ART – assisted reproduction technology (ovulation induction or in-vitro fertilization); DM – diabetes mellitus; NRFHR – non reassuring fetal heart rate.
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Table 2 Neonatal outcomes of the study groups.
Neonatal weight (grams) SGA 10th percentile Fetal demise 5-minute Apgar score 7 Umbilical cord pH 7.1 NICU admission Neonatal hypoglycemia Respiratory morbidity * Cerebral morbidity ** Neonatal sepsis Phototherapy Blood transfusions Necrotizing enterocolitis Neonatal death Composite adverse neonatal outcome
Twins with RFM n = 166
Twins no RFM n = 166
p-value
2342.5 433.6 15 (9.03) 2 (1.2) 6 (3.6) 14 (8.43) 54 (32.5) 11 (6.6) 22 (13.2) 10 (6.0) 2 (1.2) 25 (15.0) 1 (0.6) 0 (0) 3 (1.8) 49 (29.5)
2603.2 382.5 9 (5.4) 0 (0) 1 (0.6) 10 (6.0) 32 (19.2) 10 (6.0) 16 (9.6) 2 (1.2) 0 (0) 11 (6.6) 0 (0) 0 (0) 0 (0) 32 (19.2)
0.65 0.27 0.49 0.11 0.50 0.001 1.0 0.35 0.03 0.49 0.01 1.0 1.0 0.24 0.01
Continuous variables are presented as mean SD and categorical variables as n (%) NICU- neonatal intensive care unit. *Respiratory morbidity- respiratory distress syndrome, or mechanical ventilation, or need for respiratory support. **Cerebral morbidity -intra-ventricular hemorrhage (all grades), or seizures or hypoxic-ischemic encephalopathy. Values in bold are statistically significant. Composite adverse neonatal outcome – one or more of the following: hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death.
culture), phototherapy, blood transfusion, necrotizing enterocolitis (NEC), and neonatal death (death in the first 28 days of life). Statistical analysis Data were analyzed with Epi Info, version 7.0 (Centers for Disease Control and Prevention, Atlanta, GA). Continuous variables were calculated as mean standard deviation (SD) and compared using the Student’s t-test or the non-parametric Mann-Whitney test as appropriate. Categorical variables were calculated as a rate (percentage) and compared with Chi square or Fisher’s exact test as appropriate. All tests were two tailed, and the threshold for statistical significance was defined as p-value < 0.05. A multivariable regression analysis was performed to identify independent associations with adverse neonatal outcome. In this analysis composite adverse neonatal outcome served as the dependent variable while maternal age, RFM, GA at delivery, smoking, preeclampsia, DM, BMI, and SGA served as independent variables. Ethical approval was obtained from local Research Ethics Committees (0022-19-WOMC) Results The final groups consisted of 83 twin pregnancy (166 neonates) with RFM complaint in the two weeks prior delivery; all referred >34 weeks of gestation. The control group consisted of 83 twin pregnancy (166 neonates), without RFM during pregnancy, matched for maternal age and gestational age. Two neonates from the RFM group, included in the analyses, were demised at presentation. Maternal and delivery characteristics are summarized in Table 1. There were no statistically significant differences in maternal and delivery characteristics. Neonatal outcome of the study groups presented in Table 2. Neonatal birthweights, as well as the rate of birthweights <10th centile, did not differ between the groups. The rate of the primary outcome was significantly higher in the RFM group compared to the no RFM group (29.5 % vs. 19.2 %, p = 0.01). The rate of NICU admissions, cerebral morbidity, and the need for phototherapy were also significantly higher in the RFM group compared to the no RFM group (32.5 % vs. 19.2 %, p = 0.001, 6.0 % vs. 1.2 %, p = 0.03 and 15.0 % vs. 6.6 %, p = 0.01 respectively).
The results of multivariable regression analysis to identify independent associations with the adverse neonatal outcome are presented in Table 3. RFM (aOR = 1.18, 95 % CI = 1.06–2.73), and GA at delivery (aOR = 0.88, 95 % CI = 0.67–0.97) were associated with adverse neonatal outcome - independent from background confounders. Discussion To our knowledge, this is the first study that compares delivery and neonatal outcomes in twin pregnancies with and without RFM. We found a higher rate of adverse neonatal outcome, as well as NICU admissions in the RFM group, compared to the no RFM group. These findings were associated with RFM independent of all background confounders. A reduction in fetal movement may be physiological, such as during fetal sleep states, and it may also result from maternal subjective difficulty in appreciating the fetal activity, especially in twin pregnancies. However, it may be a sign of impending or existing pathology, and fetal compromise. Previous studies, in singleton pregnancies, published that up to 87 % of fetal movements are accurately perceived simultaneously by the mother when recorded using an external electromagnetic device [18,24] no comparable studies were published regarding twins. Previous studies aimed to determine the diagnostic value of fetal movements counting by the mother; some investigated the required mean time for counting fetal movements in different methods - all studies were performed on singleton pregnancies. Few studies found that fetal movement counting tests can be used as primary screening methods in predicting fetal distress, increased identification of fetal
Table 3 Results of a multivariable regression analysis for independent associations with adverse neonatal outcome. Variable
aOR
95 % CI
Maternal age Gestational age at delivery Reduced fetal movements Smoking Body mass index Preeclampsia Diabetes Mellitus Small for gestational age (SGA)
1.32 0.88 1.18 1.12 1.05 1.23 1.08 1.09
0.65-2.96 0.67-0.97 1.06-2.73 0.88-2.69 0.77-3.36 0.88-3.14 0.67-2.57 0.89-3.66
Values in bold are statistically significant.
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growth restriction, and improved perinatal outcome [25,26]. Berbey et al. studied 752 pregnancies with a gestational age of more than 35 weeks; they found that decreased fetal movements reported by the mother were significantly predictive for the abnormal results of fetal heart rate monitor or biophysical score on ultrasound and adverse pregnancy outcomes [27]. Nevertheless, some studies could not find an association between RFM and adverse neonatal outcomes. According to Harrington et al. patients, who present solely with RFM in the third trimester, without any other risk factor, do not appear to constitute a high-risk group; their pregnancy outcome is as good as that of the general population [28]. Although the numbers in this study are relatively small, their results support the Cochrane’s findings [29]. Importantly all these data are derived from singleton pregnancies, and data regarding twins are sparse. The evidence from our study indicates that a complaint of RFM during a dichorionic twin pregnancy, beyond 34 weeks of gestation, might be associated with a less favorable neonatal outcome. Consequently, these patients require further fetal assessment and tests to identify a possible fetal compromise/distress. Several strengths should be noted in the current study. First, according to our knowledge, this is the first attempt to study the association between RFM in twin pregnancies and adverse neonatal outcomes. Second, we were able to assess a relatively large cohort of 83 pregnancies and 166 neonates in each group. Third, we were able to demonstrate the association between RFM in twins and adverse neonatal outcomes independent of background confounders. Lastly, the study was performed under the circumstances of a general obstetric triage, which is probably similar in many birthing units. This strengthens the generalizability of our results. The current study is not without limitations. First, we are aware that RFM was a subjective impression of the patient, which is not well defined or standardized. Second, we have only collected short term neonatal outcomes. RFM might suggest a profound neurological or skeletal disorder. Lastly, the use of a composite outcome may be viewed as a limitation of this study. A direct biological linkage between each of the components of the composite and RFM is difficult to describe. However, we believe the use of a composite was necessary because the individual components of the composite are rare complications. We have described and validated the same composite neonatal outcomes in our previous publications with other pregnancy complications [30,31]. In conclusion, in contrast to our hypothesis, RFM in twins was independently associated with adverse neonatal outcomes. These findings may suggest that though commonly overlooked in twin pregnancies, RFM still should be considered as an "alert sign" in every obstetric triage. Future prospective studies are needed to establish the value of fetal movements counting in twin pregnancies and its ability to predict adverse neonatal outcome. Sources of financial support None Declaration of Competing Interest None. References [1] Mangesi L, Hofmeyr GJ, Smith V, Smyth RMD. Fetal movement counting for assessment of fetal wellbeing. Cochrane Database Syst Rev 2015(October (10)) CD004909. [2] Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births defined by customised versus population-based birthweight standards. BJOG 2001;108(August (8)):830–4.
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