http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–4 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.984604
ORIGINAL ARTICLE
Prospective risk of fetal death with gastroschisis Michelle R Meyer1, Brian L Shaffer2, Amy E Doss2, Alison G Cahill3, Jonathan M Snowden2, and Aaron B Caughey2 University of California at San Francisco, San Francisco, CA, USA, 2Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA, and 3Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, MO, USA
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1
Abstract
Keywords
Objective: To evaluate the ongoing risk of intrauterine fetal demise (IUFD) in fetuses with gastroschisis compared to non-anomalous fetuses. Methods: This was a retrospective cohort study of all births in the United States in 2005–2006, as recorded in the National Center for Health Statistics natality database. Risk of IUFD in fetuses with gastroschisis was compared to non-anomalous fetuses, utilizing total at-risk fetuses as the denominator. Results: Risk of IUFD in fetuses with gastroschisis was 4.5%, compared to 0.6% in nonanomalous fetuses (p50.001). When controlling for gestational age and other confounders, the adjusted odds ratio for IUFD in fetuses with gastroschisis was 7.06 (95% CI: 3.33–14.96). After 32 weeks, risk of IUFD/ongoing pregnancy was greater at each week of gestation in fetuses with gastroschisis. Conclusions: Risk of IUFD for fetuses with gastroschisis is greater than in non-anomalous fetuses. This risk increases significantly after 32 weeks’ gestation. Demographic variables are associated with higher rates of gastroschisis and ultimately IUFD. These data may be useful in consideration of timing of delivery.
Fetal death, gastroschisis, IUFD, risk
Introduction Gastroschisis is an abdominal wall defect occurring in approximately one in 5–10 000 live births [1]. Fetuses with gastroschisis are at an increased risk of fetal and neonatal death, yet prediction of poor outcomes remains challenging [2]. Overall, survival of live born infants with gastroschisis is over 90 percent [3]; however, gastroschisis is also associated with additional bowel malformations that may lead to considerable morbidity. Complex gastroschisis with concomitant jejunal (or ileal) atresia or stenosis, bowel perforation, volvulus, or even necrosis may lead to multiple surgeries, prolonged hospitalization and long-term gastrointestinal problems [4]. Additionally, gastroschisis is associated with intrauterine fetal demise (IUFD). One recent meta-analysis estimated the prevalence of IUFD in gastroschisis to be 4.5% [5]. However, existing studies of IUFD are limited to case series and relatively small cohort studies without the statistical power to examine the IUFD risk at each week of gestation. Such information is necessary to inform decisions regarding the timing of delivery, as routine late preterm or early term birth may prevent IUFD but may add to neonatal morbidity and Address for correspondence: Aaron B Caughey, MD, PhD, Professor and Chair, Department of Obstetrics and Gynecology, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA. Tel: +503 494 2999. Fax: +503 494 4473. E-mail: [email protected]
History Received 29 July 2014 Revised 27 October 2014 Accepted 29 October 2014 Published online 23 December 2014
even mortality. Current recommendations generally are to deliver fetuses with gastroschisis in the early term period at 37 or 38 weeks of gestation to avoid morbidity, mortality or term stillbirth; however, there is currently no consensus as to the optimal timing of delivery, nor is there particularly strong evidence to support early elective delivery [6]. The weekly risk of IUFD in fetuses with gastroschisis is not well described. Such information would be useful to clinicians and patients alike for decision-making regarding the optimal timing of delivery for affected fetuses. We thus designed a retrospective cohort study to investigate the weekly ongoing risk of IUFD for fetuses affected with gastroschisis.
Methods This was a retrospective cohort study of births in the United States from 2005 to 2006, as documented in the National Center for Health Statistics natality database. We analyzed births from states that utilized the 2003 revision of the US certificate of live birth, which allowed for specific identification of fetuses and neonates with gastroschisis. Inclusion criteria included singleton gestations born at 24 0/7 to 41 6/7 weeks’ gestation. Exclusion criteria included multiple gestations and anomalies other than gastroschisis. The total number of singleton births was documented, and the births were classified as either affected by gastroschisis or as nonanomalous. The number of at-risk fetuses was used as the
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
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M. R. Meyer et al.
denominator, and overall IUFD rates between the two groups were compared using the chi-square test. Multivariable logistic regression analysis was used to estimate adjusted odds of IUFD when controlling for the potential cofounders of gestational age, birthweight, race/ethnicity, parity, maternal age, education and gestational hypertension. The risk of IUFD at different gestational ages was also determined by obtaining the gestational age of each fetus, and then comparing the rates of IUFD per 10 000 ongoing pregnancies for pregnancies with isolated gastroschisis and for non-anomalous pregnancies. This model utilized the number of ongoing pregnancies as the denominator, with the number of IUFDs as the numerator. The risk of IUFD in fetuses with isolated gastroschisis was compared to the risk of IUFD in non-anomalous fetuses at each gestational age. In order to present the data in a more stable fashion, we utilized a three-point data smoothing technique, which incorporated data from the week previous to and after the given week in question in order to improve the stability of the risk estimate at a particular gestational age. Three-point smoothing estimates create an approximating function that eliminates noise from individual data points, capturing the overall pattern of the data in a smoother signal [7]. To accomplish this, the data points of IUFD rates from three consecutive weeks were added together to create a smoother estimate of the data trends. A p value of less than 0.05 was considered statistically significant. STATA software (version 11.0, College Station, TX) was utilized for all statistical analyses.
Results There were 3 101 042 singleton births documented in the database utilizing the new birth certificate form that met inclusion and exclusion criteria. 3 100 117 births were categorized as non-anomalous births, while 925 were births affected by gastroschisis. 42 (4.5%) of fetuses with gastroschisis experienced IUFD compared with 7442 (0.24%) of non-anomalous fetuses. After controlling for potential confounders (maternal age, gestational age, birthweight, parity, ethnicity, chronic hypertension, education and number of prenatal visits), the adjusted OR for IUFD was 7.06, 95% confidence interval [CI] (3.33–14.96), p50.001. Demographic information was compared between women whose fetuses had gastroschisis and those with non-anomalous fetuses (Table 1). Maternal age less than 20 was associated with an increased risk of gastroschisis (OR ¼ 2.66, 95% CI 2.17–3.24), while maternal age 35 or greater was associated with a lower rate of gastroschisis (OR ¼ 0.37, 95% CI 0.23–0.60). Race/ethnicity was also associated with risk of gastroschisis, with black women having a decreased risk of gastroschisis (OR ¼ 0.50, 95% CI 0.37–0.67). Women who smoked had approximately twice the likelihood of having a fetus with gastroschisis (OR ¼ 1.95, 95% CI 1.62–2.36). Women with at least some college were less likely to have a fetus with gastroschisis (OR ¼ 0.68, 95% CI 0.56–0.83). Nulliparity was associated with a higher risk of gastroschisis (OR ¼ 2.14, 95% CI 1.78–2.58). The IUFD rate per ongoing pregnancies was calculated for each week of gestation from 24 weeks to 41 weeks’ gestation for both pregnancies with gastroschisis and non-anomalous
J Matern Fetal Neonatal Med, Early Online: 1–4
Table 1. Demographic variables, clinical characteristics, and predictors of gastroschisis.
Demographic measure Maternal age 520 20–35 435 Race/ethnicity Caucasian Black Latina Asian Native American Other Smoking status Smoker Non-smoker Educational status Some college High school or less Gestational hypertension Gestational hypertension No gestational hypertension Parity Nulliparous Multiparous Number of prenatal visits 55 visits 5–15 visits 415 visits
Gastroschisis (%) N ¼ 925
Non-anomalous (%) N ¼ 3 099 839
37 60 3
11 75 14
50.001
62 10 23 2 1 1
54 13 27 5 1 1
50.001
26 74
13 87
50.001
30 70
49 51
50.001
2
4
0.013
98
96
65 35
40 60
50.001
30 60 10
16 77 7
50.001
p value
pregnancies (Table 2). There was a significantly higher IUFD rate for fetuses with gastroschisis compared to non-anomalous pregnancies at all gestational ages (p50.05), except for gestational ages of 28, 29, 32 and 37 weeks, in which the rates of IUFD were not significantly different. Three-point smoothing estimates were utilized to graphically illustrate the prospective fetal death risk in fetuses with gastroschisis compared to the risk in non-anomalous fetuses from weeks 25 to 40 (Table 3, Figure 1). The graphical data illustrates that overall, the risk of IUFD in gastroschisis increases with increasing gestational age, with a significant increase in IUFD risk after 38 weeks.
Discussion Fetuses with gastroschisis are more likely to experience IUFD than non-anomalous fetuses. The overall IUFD rate of 4.5% in fetuses with gastroschisis in this study is comparable to other authors’ findings from the existing literature [5]. Additionally, there is a general trend of increased risk of IUFD with increasing gestational age, with a significant increase in IUFD risk at 38 weeks and beyond, which may lead to recommended delivery by 38 weeks to prevent subsequent stillbirth. More research is needed to examine the competing risks of neonatal morbidity and mortality in the late preterm and early term periods to investigate whether routine delivery at an earlier gestational age is supported. Based on these findings and those from previous research [6], timing of delivery should be discussed during antenatal visits with patients whose fetuses are diagnosed with gastroschisis. In terms of the specific timing of delivery, the
IUFD and gastroschisis
DOI: 10.3109/14767058.2014.984604
3
Table 2. Risk of IUFD in ongoing pregnancies with gastroschisis.
Gestational age weeks weeks weeks weeks weeks weeks weeks weeks weeks
IUFD/10K ongoing pregnancies Gastroschisis
p value
1.8 1.6 1.3 1.2 1.2 1.1 1.3 1.1 1.1
45.3 34.0 22.8 45.7 11.4 0 23.1 35.1 23.9
50.001 0.026 0.031 50.001 0.061 0.544 0.040 0.002 0.059
(N ¼ 3 093 558) (N ¼ 3 090 980) (N ¼ 3 087 943) (N ¼ 3 084 562) (N ¼ 3 080 774) (N ¼ 3 075 539) (N ¼ 3 068 930) (N ¼ 3 059 759) (N ¼ 3 048 038)
Table 3. Risk of IUFD in ongoing pregnancies with gastroschisis: three-point smoothing estimates.
Gestational age 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
IUFD/10K ongoing pregnancies Non-anomalous
IUFD/10K ongoing pregnancies Gastroschisis
1.6 1.4 1.2 1.2 1.2 1.2 1.2 1.1 1.2 1.3 1.5 1.6 2.0 2.3 2.9 3.5
34.0 34.2 36.6 19.0 11.5 19.4 27.4 32.0 46.5 53.1 64.3 46.4 59.3 59.7 103.5 76.1
Prospective fetal death risk in fetuses with gastroschisis IUFD/10,000 Ongoing Pregnancies
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24 25 26 27 28 29 30 31 32
IUFD/10K ongoing pregnancies Non-anomalous
120 100
Non-anomalous Gastroschisis
80 60 40 20 0 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Gestational Age (weeks)
Figure 1. Prospective fetal death risk in fetuses with gastroschisis (using three-point smoothing estimates weighted equally by week).
current study suggests that the risk of stillbirth in fetuses with gastroschisis is greater than that associated with chronic hypertension [8] or in those complicated by cholestasis [9]. While early term and late preterm delivery can be recommended in settings with limited additional neonatal morbidity or mortality (i.e. chronic hypertension), part of the challenge in determining the optimal gestational age is ascertaining the tradeoff in neonatal morbidity and mortality of planned
delivery at each gestational age so that the clinician can compare with the ongoing risk of stillbirth. In the setting of gastroschisis, the newborn is likely to undergo surgery soon after birth; thus, the impact of respiratory distress syndrome may be even greater than in non-anomalous newborns. Therefore, future research should investigate the short-term and long-term outcomes of early elective delivery to provide proper information to ascertain the optimal gestational age of delivery. In addition, future research should investigate the role of antepartum fetal testing in the management of fetuses with gastroschisis. To date, the use of antepartum testing and fetal monitoring has only been examined in a small retrospective study of 105 cases of gastroschisis [10]. This study demonstrated that fetuses with abnormal heart tracings were more likely to undergo cesarean delivery at an earlier gestational age, but there was no difference in Apgar scores or umbilical artery pH values at birth. However, the stillbirth rate was 1.9%, which is lower than the stillbirth rate of 4.5% found in our study and in other previous research. However, given that pregnancies with an increased risk of stillbirth are often monitored with antenatal testing, such monitoring is a reasonable approach until further data better delineates the timing and frequency of such testing. Notably, there are a number of important potential confounders for stillbirth associated with gastroschisis. For example, young maternal age (520 years old), Caucasian race, smoking, receiving a high school education or less, nulliparity and attending either less than five or more than fifteen prenatal visits were all associated with higher rates of gastroschisis and are known to be associated with risk of IUFD as well. All of these potential confounders were controlled for in our multivariable model examining the risk of IUFD. This study had the strengths of a large sample size and the ability to conduct stratified analyses. For example, the model utilized afforded the ability to investigate the risks of IUFD at each gestational age, which has not previously been examined in the literature. Despite these and other strengths, the study was not without limitations. One such limitation was the retrospective study design, which limits the ability to collect ongoing data throughout gestation. Additionally, we utilized administrative data that can be limited by missing or inadequately coded data. Thus, future studies may want to use a multi-center prospective cohort study for further insight. Future research could also utilize a multi-center randomized-
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controlled trial design to investigate the impact of early elective delivery on risk of IUFD. Another limitation was the fact that the only outcome assessed was IUFD. Future research should investigate the risks of short-term and long-term neonatal outcomes, and studies could use the model implemented by this study to evaluate risks at different gestational ages. The association between gastroschisis and IUFD was confirmed by this study and we were able to demonstrate an increased risk of IUFD during later gestational ages in the third trimester. In addition, this study demonstrated associations among different demographic variables and gastroschisis. These findings have significant implications for antenatal counseling and delivery management decisions. Most importantly, our study was the first to investigate the risk of IUFD with gastroschisis using the number of ongoing pregnancies as the denominator, which could ultimately further influence counseling and decision-making during antenatal visits. Certainly, these data can be used by clinicians caring for such women to guide such decision-making week by week.
Declaration of interest The authors report no declarations of interest.
J Matern Fetal Neonatal Med, Early Online: 1–4
References 1. Mastroiacovo P, Lisi A, Castilla EE. The incidence of gastroschisis: research urgently needs resources. BMJ 2006;332:423. 2. Janoo J, Cunningham M, Hobbs GR, et al. Can antenatal ultrasounds help predict outcomes in babies born with gastroschisis? The West Virginia experience. WV Med J 2013;109:22–7. 3. Santiago-Munoz PC, McIntire DD, Barber RG, et al. Outcomes of pregnancies with fetal gastroschisis. Obstet Gynecol 2007;110: 663–8. 4. Hunter A, Soothill P. Gastroschisis – an overview. Prenat Diagn 2002;22:869–73. 5. South AP, Stutey KM, Meinzen-Derr J. Metaanalysis of the prevalence of intrauterine fetal death in gastroschisis. Am J Obstet Gynecol 2013;209:114.e1–13. 6. Baud D, Lausman A, Alfaraj MA, et al. Expectant management compared with elective delivery at 37 weeks for gastroschisis. Obstet Gynecol 2013;121:990–8. 7. Graham MM. Physiologic smoothing of blood time-activity curves for PET data analysis. J Nucl Med 1997;38:1161–8. 8. Yanit K, Snowden J, Cheng YW, Caughey AB. The impact of chronic hypertension and pregestational diabetes on pregnancy outcomes. Am J Obstet Gynecol 2012;207:333.e1–6. 9. Geenes V, Chappell LC, Seed PT, et al. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology 2014;59:1482–91. 10. Kuleva M, Salomon LJ, Benoist G, et al. The value of daily fetal heart rate home monitoring in addition to serial ultrasound examinations in pregnancies complicated by fetal gastroschisis. Prenat Diagn 2012;32:789–96.
ORIGINAL ARTICLE
Prospective risk of fetal death with gastroschisis Michelle R Meyer1, Brian L Shaffer2, Amy E Doss2, Alison G Cahill3, Jonathan M Snowden2, and Aaron B Caughey2 University of California at San Francisco, San Francisco, CA, USA, 2Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA, and 3Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, MO, USA
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1
Abstract
Keywords
Objective: To evaluate the ongoing risk of intrauterine fetal demise (IUFD) in fetuses with gastroschisis compared to non-anomalous fetuses. Methods: This was a retrospective cohort study of all births in the United States in 2005–2006, as recorded in the National Center for Health Statistics natality database. Risk of IUFD in fetuses with gastroschisis was compared to non-anomalous fetuses, utilizing total at-risk fetuses as the denominator. Results: Risk of IUFD in fetuses with gastroschisis was 4.5%, compared to 0.6% in nonanomalous fetuses (p50.001). When controlling for gestational age and other confounders, the adjusted odds ratio for IUFD in fetuses with gastroschisis was 7.06 (95% CI: 3.33–14.96). After 32 weeks, risk of IUFD/ongoing pregnancy was greater at each week of gestation in fetuses with gastroschisis. Conclusions: Risk of IUFD for fetuses with gastroschisis is greater than in non-anomalous fetuses. This risk increases significantly after 32 weeks’ gestation. Demographic variables are associated with higher rates of gastroschisis and ultimately IUFD. These data may be useful in consideration of timing of delivery.
Fetal death, gastroschisis, IUFD, risk
Introduction Gastroschisis is an abdominal wall defect occurring in approximately one in 5–10 000 live births [1]. Fetuses with gastroschisis are at an increased risk of fetal and neonatal death, yet prediction of poor outcomes remains challenging [2]. Overall, survival of live born infants with gastroschisis is over 90 percent [3]; however, gastroschisis is also associated with additional bowel malformations that may lead to considerable morbidity. Complex gastroschisis with concomitant jejunal (or ileal) atresia or stenosis, bowel perforation, volvulus, or even necrosis may lead to multiple surgeries, prolonged hospitalization and long-term gastrointestinal problems [4]. Additionally, gastroschisis is associated with intrauterine fetal demise (IUFD). One recent meta-analysis estimated the prevalence of IUFD in gastroschisis to be 4.5% [5]. However, existing studies of IUFD are limited to case series and relatively small cohort studies without the statistical power to examine the IUFD risk at each week of gestation. Such information is necessary to inform decisions regarding the timing of delivery, as routine late preterm or early term birth may prevent IUFD but may add to neonatal morbidity and Address for correspondence: Aaron B Caughey, MD, PhD, Professor and Chair, Department of Obstetrics and Gynecology, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA. Tel: +503 494 2999. Fax: +503 494 4473. E-mail: [email protected]
History Received 29 July 2014 Revised 27 October 2014 Accepted 29 October 2014 Published online 23 December 2014
even mortality. Current recommendations generally are to deliver fetuses with gastroschisis in the early term period at 37 or 38 weeks of gestation to avoid morbidity, mortality or term stillbirth; however, there is currently no consensus as to the optimal timing of delivery, nor is there particularly strong evidence to support early elective delivery [6]. The weekly risk of IUFD in fetuses with gastroschisis is not well described. Such information would be useful to clinicians and patients alike for decision-making regarding the optimal timing of delivery for affected fetuses. We thus designed a retrospective cohort study to investigate the weekly ongoing risk of IUFD for fetuses affected with gastroschisis.
Methods This was a retrospective cohort study of births in the United States from 2005 to 2006, as documented in the National Center for Health Statistics natality database. We analyzed births from states that utilized the 2003 revision of the US certificate of live birth, which allowed for specific identification of fetuses and neonates with gastroschisis. Inclusion criteria included singleton gestations born at 24 0/7 to 41 6/7 weeks’ gestation. Exclusion criteria included multiple gestations and anomalies other than gastroschisis. The total number of singleton births was documented, and the births were classified as either affected by gastroschisis or as nonanomalous. The number of at-risk fetuses was used as the
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
2
M. R. Meyer et al.
denominator, and overall IUFD rates between the two groups were compared using the chi-square test. Multivariable logistic regression analysis was used to estimate adjusted odds of IUFD when controlling for the potential cofounders of gestational age, birthweight, race/ethnicity, parity, maternal age, education and gestational hypertension. The risk of IUFD at different gestational ages was also determined by obtaining the gestational age of each fetus, and then comparing the rates of IUFD per 10 000 ongoing pregnancies for pregnancies with isolated gastroschisis and for non-anomalous pregnancies. This model utilized the number of ongoing pregnancies as the denominator, with the number of IUFDs as the numerator. The risk of IUFD in fetuses with isolated gastroschisis was compared to the risk of IUFD in non-anomalous fetuses at each gestational age. In order to present the data in a more stable fashion, we utilized a three-point data smoothing technique, which incorporated data from the week previous to and after the given week in question in order to improve the stability of the risk estimate at a particular gestational age. Three-point smoothing estimates create an approximating function that eliminates noise from individual data points, capturing the overall pattern of the data in a smoother signal [7]. To accomplish this, the data points of IUFD rates from three consecutive weeks were added together to create a smoother estimate of the data trends. A p value of less than 0.05 was considered statistically significant. STATA software (version 11.0, College Station, TX) was utilized for all statistical analyses.
Results There were 3 101 042 singleton births documented in the database utilizing the new birth certificate form that met inclusion and exclusion criteria. 3 100 117 births were categorized as non-anomalous births, while 925 were births affected by gastroschisis. 42 (4.5%) of fetuses with gastroschisis experienced IUFD compared with 7442 (0.24%) of non-anomalous fetuses. After controlling for potential confounders (maternal age, gestational age, birthweight, parity, ethnicity, chronic hypertension, education and number of prenatal visits), the adjusted OR for IUFD was 7.06, 95% confidence interval [CI] (3.33–14.96), p50.001. Demographic information was compared between women whose fetuses had gastroschisis and those with non-anomalous fetuses (Table 1). Maternal age less than 20 was associated with an increased risk of gastroschisis (OR ¼ 2.66, 95% CI 2.17–3.24), while maternal age 35 or greater was associated with a lower rate of gastroschisis (OR ¼ 0.37, 95% CI 0.23–0.60). Race/ethnicity was also associated with risk of gastroschisis, with black women having a decreased risk of gastroschisis (OR ¼ 0.50, 95% CI 0.37–0.67). Women who smoked had approximately twice the likelihood of having a fetus with gastroschisis (OR ¼ 1.95, 95% CI 1.62–2.36). Women with at least some college were less likely to have a fetus with gastroschisis (OR ¼ 0.68, 95% CI 0.56–0.83). Nulliparity was associated with a higher risk of gastroschisis (OR ¼ 2.14, 95% CI 1.78–2.58). The IUFD rate per ongoing pregnancies was calculated for each week of gestation from 24 weeks to 41 weeks’ gestation for both pregnancies with gastroschisis and non-anomalous
J Matern Fetal Neonatal Med, Early Online: 1–4
Table 1. Demographic variables, clinical characteristics, and predictors of gastroschisis.
Demographic measure Maternal age 520 20–35 435 Race/ethnicity Caucasian Black Latina Asian Native American Other Smoking status Smoker Non-smoker Educational status Some college High school or less Gestational hypertension Gestational hypertension No gestational hypertension Parity Nulliparous Multiparous Number of prenatal visits 55 visits 5–15 visits 415 visits
Gastroschisis (%) N ¼ 925
Non-anomalous (%) N ¼ 3 099 839
37 60 3
11 75 14
50.001
62 10 23 2 1 1
54 13 27 5 1 1
50.001
26 74
13 87
50.001
30 70
49 51
50.001
2
4
0.013
98
96
65 35
40 60
50.001
30 60 10
16 77 7
50.001
p value
pregnancies (Table 2). There was a significantly higher IUFD rate for fetuses with gastroschisis compared to non-anomalous pregnancies at all gestational ages (p50.05), except for gestational ages of 28, 29, 32 and 37 weeks, in which the rates of IUFD were not significantly different. Three-point smoothing estimates were utilized to graphically illustrate the prospective fetal death risk in fetuses with gastroschisis compared to the risk in non-anomalous fetuses from weeks 25 to 40 (Table 3, Figure 1). The graphical data illustrates that overall, the risk of IUFD in gastroschisis increases with increasing gestational age, with a significant increase in IUFD risk after 38 weeks.
Discussion Fetuses with gastroschisis are more likely to experience IUFD than non-anomalous fetuses. The overall IUFD rate of 4.5% in fetuses with gastroschisis in this study is comparable to other authors’ findings from the existing literature [5]. Additionally, there is a general trend of increased risk of IUFD with increasing gestational age, with a significant increase in IUFD risk at 38 weeks and beyond, which may lead to recommended delivery by 38 weeks to prevent subsequent stillbirth. More research is needed to examine the competing risks of neonatal morbidity and mortality in the late preterm and early term periods to investigate whether routine delivery at an earlier gestational age is supported. Based on these findings and those from previous research [6], timing of delivery should be discussed during antenatal visits with patients whose fetuses are diagnosed with gastroschisis. In terms of the specific timing of delivery, the
IUFD and gastroschisis
DOI: 10.3109/14767058.2014.984604
3
Table 2. Risk of IUFD in ongoing pregnancies with gastroschisis.
Gestational age weeks weeks weeks weeks weeks weeks weeks weeks weeks
IUFD/10K ongoing pregnancies Gastroschisis
p value
1.8 1.6 1.3 1.2 1.2 1.1 1.3 1.1 1.1
45.3 34.0 22.8 45.7 11.4 0 23.1 35.1 23.9
50.001 0.026 0.031 50.001 0.061 0.544 0.040 0.002 0.059
(N ¼ 3 093 558) (N ¼ 3 090 980) (N ¼ 3 087 943) (N ¼ 3 084 562) (N ¼ 3 080 774) (N ¼ 3 075 539) (N ¼ 3 068 930) (N ¼ 3 059 759) (N ¼ 3 048 038)
Table 3. Risk of IUFD in ongoing pregnancies with gastroschisis: three-point smoothing estimates.
Gestational age 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
IUFD/10K ongoing pregnancies Non-anomalous
IUFD/10K ongoing pregnancies Gastroschisis
1.6 1.4 1.2 1.2 1.2 1.2 1.2 1.1 1.2 1.3 1.5 1.6 2.0 2.3 2.9 3.5
34.0 34.2 36.6 19.0 11.5 19.4 27.4 32.0 46.5 53.1 64.3 46.4 59.3 59.7 103.5 76.1
Prospective fetal death risk in fetuses with gastroschisis IUFD/10,000 Ongoing Pregnancies
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24 25 26 27 28 29 30 31 32
IUFD/10K ongoing pregnancies Non-anomalous
120 100
Non-anomalous Gastroschisis
80 60 40 20 0 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Gestational Age (weeks)
Figure 1. Prospective fetal death risk in fetuses with gastroschisis (using three-point smoothing estimates weighted equally by week).
current study suggests that the risk of stillbirth in fetuses with gastroschisis is greater than that associated with chronic hypertension [8] or in those complicated by cholestasis [9]. While early term and late preterm delivery can be recommended in settings with limited additional neonatal morbidity or mortality (i.e. chronic hypertension), part of the challenge in determining the optimal gestational age is ascertaining the tradeoff in neonatal morbidity and mortality of planned
delivery at each gestational age so that the clinician can compare with the ongoing risk of stillbirth. In the setting of gastroschisis, the newborn is likely to undergo surgery soon after birth; thus, the impact of respiratory distress syndrome may be even greater than in non-anomalous newborns. Therefore, future research should investigate the short-term and long-term outcomes of early elective delivery to provide proper information to ascertain the optimal gestational age of delivery. In addition, future research should investigate the role of antepartum fetal testing in the management of fetuses with gastroschisis. To date, the use of antepartum testing and fetal monitoring has only been examined in a small retrospective study of 105 cases of gastroschisis [10]. This study demonstrated that fetuses with abnormal heart tracings were more likely to undergo cesarean delivery at an earlier gestational age, but there was no difference in Apgar scores or umbilical artery pH values at birth. However, the stillbirth rate was 1.9%, which is lower than the stillbirth rate of 4.5% found in our study and in other previous research. However, given that pregnancies with an increased risk of stillbirth are often monitored with antenatal testing, such monitoring is a reasonable approach until further data better delineates the timing and frequency of such testing. Notably, there are a number of important potential confounders for stillbirth associated with gastroschisis. For example, young maternal age (520 years old), Caucasian race, smoking, receiving a high school education or less, nulliparity and attending either less than five or more than fifteen prenatal visits were all associated with higher rates of gastroschisis and are known to be associated with risk of IUFD as well. All of these potential confounders were controlled for in our multivariable model examining the risk of IUFD. This study had the strengths of a large sample size and the ability to conduct stratified analyses. For example, the model utilized afforded the ability to investigate the risks of IUFD at each gestational age, which has not previously been examined in the literature. Despite these and other strengths, the study was not without limitations. One such limitation was the retrospective study design, which limits the ability to collect ongoing data throughout gestation. Additionally, we utilized administrative data that can be limited by missing or inadequately coded data. Thus, future studies may want to use a multi-center prospective cohort study for further insight. Future research could also utilize a multi-center randomized-
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controlled trial design to investigate the impact of early elective delivery on risk of IUFD. Another limitation was the fact that the only outcome assessed was IUFD. Future research should investigate the risks of short-term and long-term neonatal outcomes, and studies could use the model implemented by this study to evaluate risks at different gestational ages. The association between gastroschisis and IUFD was confirmed by this study and we were able to demonstrate an increased risk of IUFD during later gestational ages in the third trimester. In addition, this study demonstrated associations among different demographic variables and gastroschisis. These findings have significant implications for antenatal counseling and delivery management decisions. Most importantly, our study was the first to investigate the risk of IUFD with gastroschisis using the number of ongoing pregnancies as the denominator, which could ultimately further influence counseling and decision-making during antenatal visits. Certainly, these data can be used by clinicians caring for such women to guide such decision-making week by week.
Declaration of interest The authors report no declarations of interest.
J Matern Fetal Neonatal Med, Early Online: 1–4
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