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Relationship between neonatal gastroschisis and maternal body mass index in a United Kingdom population
Accepted Manuscript Title: Relationship between neonatal gastroschisis and maternal body mass index in a Uinted Kingdom population Author: Joann Hale Abigail Derbyshire Alexander Taylor Clive Osmond Diana Wellesley David T. Howe PII: DOI: Reference:
S0301-2115(16)31077-6 http://dx.doi.org/doi:10.1016/j.ejogrb.2016.12.015 EURO 9713
To appear in:
EURO
Received date: Revised date: Accepted date:
20-9-2016 12-12-2016 14-12-2016
Please cite this article as: Hale Joann, Derbyshire Abigail, Taylor Alexander, Osmond Clive, Wellesley Diana, Howe David T.Relationship between neonatal gastroschisis and maternal body mass index in a Uinted Kingdom population.European Journal of Obstetrics and Gynecology and Reproductive Biology http://dx.doi.org/10.1016/j.ejogrb.2016.12.015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
RELATIONSHIP BETWEEN NEONATAL GASTROSCHISIS AND MATERNAL BMI IN A UK POPULATION Short Title: - Gastroschisis and BMI in a UK population 1. Joann Hale Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK [email protected] Tel: -07876571312 Fax No: - 02381 206207 2. Abigail Derbyshire Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK 3. Alexander Taylor Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK 4. Clive Osmond Medical Research Council Lifecourse Epidemiology Unit, University Hospital Southampton, Tremona Road, Southampton, S016 6YD, UK 5. Diana Wellesley Department of Clinical Genetics, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, UK 6. David T Howe Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK
ABSTRACT
Objective It has been reported that gastroschisis is associated with low maternal body mass index (BMI). We tested this hypothesis in the UK.
Study Design
We studied cases of gastroschisis ascertained from the regional fetal congenital anomaly register. We compared each affected mother with two controls from the birth register and maternity database. The first control was the next mother to deliver in the hospital, representing the normal population of mothers. The second control was the next mother to deliver an unaffected child whose age was within one year of that of the index case controlling for maternal age.
Results There was a strong inverse association between maternal age and gastroschisis.
An inverse association between gastroschisis and birth order was eliminated by adjustment for maternal age.
The average age of mothers of affected children was 22.1years; of the next delivery control was 28.8years, and of the age matched control was 22.2 years.
A weak non-statistically significant negative association between BMI and gastroschisis was further weakened by adjustment for maternal age.
Conclusion Our results confirm the previously reported association between low maternal age and gastroschisis but suggest that within our UK population the link between low BMI and gastroschisis reported elsewhere is explained by younger mothers being thinner.
Keywords : Gastroschisis, Maternal Age, Maternal BMI
Relationship between neonatal gastroschisis and maternal body mass index in a United Kingdom population
Hale J, Derbyshire A, Taylor A, Osmond C, Wellesley D, Howe David T
INTRODUCTION
Gastroschisis is a congenital defect of the abdominal wall with paraumbilical herniation of the abdominal organs. It is usually an isolated structural defect that is not associated with chromosomal abnormalities. The prevalence is quoted as being 1 to 5.1 per 10,000 live births; although more recent data has documented a worldwide but not universally increasing rate[1]. This further strengthens the case for a study into the risk factors for the condition.
There is substantial disagreement regarding the developmental pathogenesis of gastroschisis[2], but a number of risk factors have been identified that appear to confer susceptibility. These include young maternal age[3-4], lower pre-pregnancy body mass index (BMI)[4], use of vasoactive medications[5], aspirin intake[6], use of drugs of abuse and smoking[7-8] and genetic polymorphisms[9]. Maternal age and BMI have been suggested to be particularly significant risk factors in the North American population[3]. The link between maternal BMI and gastroschisis has not been investigated in the United Kingdom and we wished to examine whether the same relationship
was present here. Our hypothesis was that low maternal BMI is associated with an increased risk of gastroschisis in UK mothers.
MATERIAL AND METHODS
All cases of gastroschisis seen in the Wessex Fetal Medicine Unit at the Princess Anne Hospital, Southampton between September 2005 and December 2014 were identified by searching our regional congenital anomaly database - WANDA (Wessex Antenatally Detected Anomalies).
The
database captures and records both antenatally and postnatally detected congenital anomalies for live births, stillbirths and terminations of pregnancy in the former Wessex health region, which covers ten maternity services in central southern England and the Channel Islands.
The data are obtained prospectively from the single regional fetal medicine unit on a weekly basis and from the neonatologists, surgeons, and pathologists on a monthly basis, as well as from referrals to the Genetics service.
Each of these specialties covers the Wessex region and sees
virtually all cases detected within this area, so ascertainment rates are high. In addition, there are regular meetings with paediatricians and those carrying out prenatal diagnosis in the regional referral hospitals.
Ethics approval to maintain and use the data in this register has been obtained from the Trent Multicentre Research Ethics Committee (Ethics number 09/H0405/48).
The cases were compared with two control groups from the birth register and maternity delivery database at the Princess Anne Hospital in Southampton. These data were collected retrospectively.
The first control group was
intended to represent the normal population of mothers delivering in the hospital. It consisted of the next mother in the register after each case to deliver an infant without gastroschisis. The second group was intended to be age-matched to the mothers of cases, in order to test the hypothetical link with BMI without confounding by maternal age. It consisted of the next mother delivered after each case, whose age was within one year, and who had an unaffected infant. We recorded the BMI calculated at booking as weight in kilograms divided by height in metres squared.
There were no multiple
pregnancies in the cases.
Statistical analysis We first produced descriptive data for the case and control groups. We crosstabulated age and BMI groups with the case and control groups. For a formal analysis of the association of age and BMI with presence of gastroschisis we use multiple conditional logistic regression analysis. Age and BMI were both right-skewed in distribution and we analysed them after log-transformation.
Including both terms assesses their joint contribution. SPSS version 21 was used for the analysis.
RESULTS
There were one hundred and twenty five cases of gastroschisis detected at the Princess Anne Hospital during the study period.
Ten cases were
excluded as there was incomplete information due to delivery at another hospital, which included the only case of intra-uterine fetal death. There were therefore 115 cases of gastroschisis included in the study and within this group there were two patients that opted for termination of pregnancy. Each control group had 115 participants. The total number of women included in the study was therefore three hundred and forty five.
Table 1 gives descriptive data for age and BMI in the case and control groups.
Table 1 illustrates the association with age by showing the numbers in fixed age groups. By design the case and age-matched control group have similar distributions. However the next-delivery controls are much less likely than cases to be under age 25 years and more likely to be 30 years and over.
Table 1 describes the association of BMI within the 3 groups and demonstrates that the majority of cases affected by gastroschsis were born to mothers with a BMI under 25 (kg/m 2).
The number of cases that were
affected and had a BMI of less than 20 was 11.3%, that had a BMI of 20-22.5 was 23% and those that had a BMI 22.5-25 was 33.9%.
Table 1 also shows the distribution of the data in relation to parity. In the group carrying a fetus with gastroschisis the majority of patients were in their first pregnancy. 64 % of cases affected with gastroschisis were in their first pregnancy, compared with 40% in the next delivery control group and 57% in the age matched control group.
The results of the conditional logistic regression analysis are shown in Table 2.
Using all the controls, there is a strong inverse association between maternal age and gastroschisis (model 1). There is a weak non-statistically significant association between BMI and gastroschisis (model 2).
This is further
weakened by adjustment for maternal age (model 3), suggesting that what association there is may be explained by the positive but weak association between maternal age and BMI (r=0.14, p<0.001). The association between maternal age and gastroschisis is scarcely affected by the BMI adjustment in model 3 (table 2). Models 4 to 9 (table 2) show results separately for the two control groups. By design there is little power to detect an age effect using age-matched controls, though the direction of effect is similar.
Using
interaction tests, there was no suggestion that there were BMI effects in younger or older mothers (data not shown).
COMMENTS
Our results confirm the previously reported association between low maternal age and gastroschisis but suggest that within our UK population the apparent link between low BMI and gastroschisis reported elsewhere is because younger mothers are thinner, rather than because of a direct effect.
Using a case control method allowed us to investigate a rare condition but the retrospective nature of our data collection means that other confounding factors such as smoking history, recreational drug use or medications and medical history may not be included.
A possible weakness or our study is
that mothers with affected fetuses were referred to the Princess Anne Hospital from hospitals across the Wessex health region, whereas all controls were taken from deliveries within the tertiary unit. However there are not great differences in the age structure, ethnicity or social class of women booked at different hospitals in Wessex so it is unlikely this would materially affect our results.
Our study used measured height and weight at pregnancy booking to calculate BMI. This differs from some papers[3] that use self-reported weight to estimate pre-pregnancy BMI. We believe that using measured weight is likely to be more accurate, because the measurements were taken in early pregnancy they were likely to be little-changed from before pregnancy, and that any change there was is likely to be consistent across all study groups.
American studies have found lower BMI to be associated with a higher risk of gastroschisis[3-4], after controlling for multiple confounders including age, in case groups of 464 and 104 infants respectively, although the larger study does note that the increased risk associated with low age is not offset by an increased bodyweight until very high BMIs are reached. One implication of this observation is that there may be some relationship to biological immaturity in the pregnancy state that may lead to development of this birth defect, as opposed to a lower BMI being simply a proxy of under nutrition[3-4].
Paranjothi et al[10] also investigated the link between maternal nutrition and gastroschisis in a UK population comparing mothers with affected fetuses with age-matched controls.
Like Siega-Riz et al[3] and Lam et al[4] they
found BMI was associated with a lower risk of gastroschisis only when the mother was obese (BMI > 30kg/m2). Thus the greatest influence on risk of gastroschisis appears to be low maternal age. Further studies are needed to investigate how these are linked.
ACKNOWLEDGEMENTS
We would like to thank Sally Boxall Nurse Specialist in Wessex Fetal Medicine Department for help with access to the WANDA Database.
DISCLOSURE
To my knowledge there are no competing interests and no individuals or companies that have financially contributed to this study.
References 1
Mastroiacovo P, Lisi A, Castilla EE. The incidence of gastroschisis: Research urgently needs resources. BMJ 2006;332:423–424 2
Stevenson RE, Rogers RC, Chandler JC, Gauderer MWL, Hunter AGW. Escape of the yolk sac: a hypothesis to explain the embryogenesis of gastroschisis. Clin Genet 2009;75:326–333 3
Siega-Riz AM, Herring AH, Olshan AF, Smith J, Moore C. The joint effects of maternal prepregnancy body mass index and age on the risk of gastroschisis. Paediatric and perinatal epidemiology 2008;23:51-57. 4
Lam PK, Torfs CP, Brand RJ. A low pre-pregnancy body mass index is a risk factor for an offspring with gastroschisis Epidemiology 1999;10:717-721. 5
Torfs CP, Katz EA, Bateson TF, Lam PK, Curry CJR. Maternal medications and environmental exposures as risk factors for gastroschisis. Teratology 1996;54:84–92. 6
Kozer E, Nikfar S, Costei A, Boskovic R, Nulman I, Koren G. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: A meta-analysis. Am J Obstet and Gynaecol 2002;187:6:1623-1630. 7
Torfs CP, Velie EM, Oechsli FW, Bateson TF, Curry CJR. A populationbased study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 1994;50:44–53. 8
Drongowski RA, Smith RK, Coran AG, Klein MD. Contribution of demographic and environmental factors to the etiology of gastroschisis: a hypothesis. Fetal Diagn Ther 1991; 6:14–27 9
Torfs CP, Christianson RE, Lovannisci DM, Shaw GM, Lammer EJ. Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis. Birth defects research (Part A): Clinical and Molecular Teratology 2006;76:723-730 10
Paranjothy S, Broughton H, Evans A, Huddart S, Drayton M, Jefferson R, Rankin J, Draper E, Cameron A, Palmer SR. The role of maternal nutrition in the aetiology of gastroschisis: an incident case-control study. International Journal of Epidemiology 2012; 41:1141-1152
Table 1 – Distribution of cases and controls by Age, BMI and Parity
Cases Mother’s Age (Years) <19 20-24 25-29 30-34 35+ Total Mean S.D. Min Age Max Age Mother’s BMI (kg/m2) <20 20-22.5 22.5-25 25-30 30+ Total Mean S.D. Min BMI Max BMI Parity Pregnancy Number 1 2 3+ All
% (n)
Next Delivery Controls % (n)
Age-Match Controls % (n)
37.4 (43) 38.3 (44) 15.7 (18) 5.2 (6) 3.5 (4) 100 (115) 22.1 5.0 14.7 40.0
9.6 (11) 20.9 (24) 23.5 (27) 32.2 (37) 13.9 (16) 100 (115) 28.8 6.1 16.8 41.7
38.3 (44) 37.4 (43) 16.5 (19) 4.3 (5) 3.5 (4) 100 (115) 22.2 5.0 14.8 40.0
% (n)
% (n)
% (n)
11.3 (13) 20.0 (23) 33.9 (39) 24.3 (28) 10.4 (12) 100 (115) 24.4 3.9 16.7 36.8
7.8 (9) 24.3 (28) 24.3 (28) 21.7 (25) 21.7 (25) 100 (115) 25.8 5.6 16.5 47.6
16.7 (19) 21.9 (25) 27.2 (31) 20.2 (23) 14.0 (16) 100 (114) 24.7 5.2 16.9 42.9
% (n)
% (n)
% (n)
64 (74) 21 (24) 15 (17) 100 (115)
40 (46) 22 (25) 38 (44) 100 (115)
57 (65) 26 (30) 17 (20) 100 (115)
Table 2 - Odds ratio for gastroschisis according to age, body mass index (BMI) and control type.
Model
All Control Pool 1 2 3
Next Delivery Controls 4 5 6
Age Match Controls 7 8 9
Predictor
Odds Ratio (OR)
95% Confidence Intervals
P value
Age (In Years) BMI (In kg/m2) Age (In Years) BMI (In kg/m2)
0.02 0.45 0.02 0.84
0.004-0.11 0.13-1.56 0.004-0.12 0.22-3.28
<0.001 0.21 <0.001 0.80
Age (In Years) BMI (In kg/m2) Age (In Years) BMI (In kg/m2)
0.007 0.24 0.008 0.81
0.001-0.004 0.05-1.05 0.001-0.04 0.12-5.69
<0.001 0.06 <0.001 0.83
Age (In Years) BMI (In kg/m2) Age (In Years) BMI (In kg/m2)
0.02 0.85 0.02 0.84
0.000-281 0.19-3.77 0.000-295 0.19-3.76
0.41 0.83 0.41 0.82
S0301-2115(16)31077-6 http://dx.doi.org/doi:10.1016/j.ejogrb.2016.12.015 EURO 9713
To appear in:
EURO
Received date: Revised date: Accepted date:
20-9-2016 12-12-2016 14-12-2016
Please cite this article as: Hale Joann, Derbyshire Abigail, Taylor Alexander, Osmond Clive, Wellesley Diana, Howe David T.Relationship between neonatal gastroschisis and maternal body mass index in a Uinted Kingdom population.European Journal of Obstetrics and Gynecology and Reproductive Biology http://dx.doi.org/10.1016/j.ejogrb.2016.12.015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
RELATIONSHIP BETWEEN NEONATAL GASTROSCHISIS AND MATERNAL BMI IN A UK POPULATION Short Title: - Gastroschisis and BMI in a UK population 1. Joann Hale Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK [email protected] Tel: -07876571312 Fax No: - 02381 206207 2. Abigail Derbyshire Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK 3. Alexander Taylor Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK 4. Clive Osmond Medical Research Council Lifecourse Epidemiology Unit, University Hospital Southampton, Tremona Road, Southampton, S016 6YD, UK 5. Diana Wellesley Department of Clinical Genetics, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, UK 6. David T Howe Department of Fetal Medicine, Princess Anne Hospital, Coxford Road, Southampton, S016 5YA, UK
ABSTRACT
Objective It has been reported that gastroschisis is associated with low maternal body mass index (BMI). We tested this hypothesis in the UK.
Study Design
We studied cases of gastroschisis ascertained from the regional fetal congenital anomaly register. We compared each affected mother with two controls from the birth register and maternity database. The first control was the next mother to deliver in the hospital, representing the normal population of mothers. The second control was the next mother to deliver an unaffected child whose age was within one year of that of the index case controlling for maternal age.
Results There was a strong inverse association between maternal age and gastroschisis.
An inverse association between gastroschisis and birth order was eliminated by adjustment for maternal age.
The average age of mothers of affected children was 22.1years; of the next delivery control was 28.8years, and of the age matched control was 22.2 years.
A weak non-statistically significant negative association between BMI and gastroschisis was further weakened by adjustment for maternal age.
Conclusion Our results confirm the previously reported association between low maternal age and gastroschisis but suggest that within our UK population the link between low BMI and gastroschisis reported elsewhere is explained by younger mothers being thinner.
Keywords : Gastroschisis, Maternal Age, Maternal BMI
Relationship between neonatal gastroschisis and maternal body mass index in a United Kingdom population
Hale J, Derbyshire A, Taylor A, Osmond C, Wellesley D, Howe David T
INTRODUCTION
Gastroschisis is a congenital defect of the abdominal wall with paraumbilical herniation of the abdominal organs. It is usually an isolated structural defect that is not associated with chromosomal abnormalities. The prevalence is quoted as being 1 to 5.1 per 10,000 live births; although more recent data has documented a worldwide but not universally increasing rate[1]. This further strengthens the case for a study into the risk factors for the condition.
There is substantial disagreement regarding the developmental pathogenesis of gastroschisis[2], but a number of risk factors have been identified that appear to confer susceptibility. These include young maternal age[3-4], lower pre-pregnancy body mass index (BMI)[4], use of vasoactive medications[5], aspirin intake[6], use of drugs of abuse and smoking[7-8] and genetic polymorphisms[9]. Maternal age and BMI have been suggested to be particularly significant risk factors in the North American population[3]. The link between maternal BMI and gastroschisis has not been investigated in the United Kingdom and we wished to examine whether the same relationship
was present here. Our hypothesis was that low maternal BMI is associated with an increased risk of gastroschisis in UK mothers.
MATERIAL AND METHODS
All cases of gastroschisis seen in the Wessex Fetal Medicine Unit at the Princess Anne Hospital, Southampton between September 2005 and December 2014 were identified by searching our regional congenital anomaly database - WANDA (Wessex Antenatally Detected Anomalies).
The
database captures and records both antenatally and postnatally detected congenital anomalies for live births, stillbirths and terminations of pregnancy in the former Wessex health region, which covers ten maternity services in central southern England and the Channel Islands.
The data are obtained prospectively from the single regional fetal medicine unit on a weekly basis and from the neonatologists, surgeons, and pathologists on a monthly basis, as well as from referrals to the Genetics service.
Each of these specialties covers the Wessex region and sees
virtually all cases detected within this area, so ascertainment rates are high. In addition, there are regular meetings with paediatricians and those carrying out prenatal diagnosis in the regional referral hospitals.
Ethics approval to maintain and use the data in this register has been obtained from the Trent Multicentre Research Ethics Committee (Ethics number 09/H0405/48).
The cases were compared with two control groups from the birth register and maternity delivery database at the Princess Anne Hospital in Southampton. These data were collected retrospectively.
The first control group was
intended to represent the normal population of mothers delivering in the hospital. It consisted of the next mother in the register after each case to deliver an infant without gastroschisis. The second group was intended to be age-matched to the mothers of cases, in order to test the hypothetical link with BMI without confounding by maternal age. It consisted of the next mother delivered after each case, whose age was within one year, and who had an unaffected infant. We recorded the BMI calculated at booking as weight in kilograms divided by height in metres squared.
There were no multiple
pregnancies in the cases.
Statistical analysis We first produced descriptive data for the case and control groups. We crosstabulated age and BMI groups with the case and control groups. For a formal analysis of the association of age and BMI with presence of gastroschisis we use multiple conditional logistic regression analysis. Age and BMI were both right-skewed in distribution and we analysed them after log-transformation.
Including both terms assesses their joint contribution. SPSS version 21 was used for the analysis.
RESULTS
There were one hundred and twenty five cases of gastroschisis detected at the Princess Anne Hospital during the study period.
Ten cases were
excluded as there was incomplete information due to delivery at another hospital, which included the only case of intra-uterine fetal death. There were therefore 115 cases of gastroschisis included in the study and within this group there were two patients that opted for termination of pregnancy. Each control group had 115 participants. The total number of women included in the study was therefore three hundred and forty five.
Table 1 gives descriptive data for age and BMI in the case and control groups.
Table 1 illustrates the association with age by showing the numbers in fixed age groups. By design the case and age-matched control group have similar distributions. However the next-delivery controls are much less likely than cases to be under age 25 years and more likely to be 30 years and over.
Table 1 describes the association of BMI within the 3 groups and demonstrates that the majority of cases affected by gastroschsis were born to mothers with a BMI under 25 (kg/m 2).
The number of cases that were
affected and had a BMI of less than 20 was 11.3%, that had a BMI of 20-22.5 was 23% and those that had a BMI 22.5-25 was 33.9%.
Table 1 also shows the distribution of the data in relation to parity. In the group carrying a fetus with gastroschisis the majority of patients were in their first pregnancy. 64 % of cases affected with gastroschisis were in their first pregnancy, compared with 40% in the next delivery control group and 57% in the age matched control group.
The results of the conditional logistic regression analysis are shown in Table 2.
Using all the controls, there is a strong inverse association between maternal age and gastroschisis (model 1). There is a weak non-statistically significant association between BMI and gastroschisis (model 2).
This is further
weakened by adjustment for maternal age (model 3), suggesting that what association there is may be explained by the positive but weak association between maternal age and BMI (r=0.14, p<0.001). The association between maternal age and gastroschisis is scarcely affected by the BMI adjustment in model 3 (table 2). Models 4 to 9 (table 2) show results separately for the two control groups. By design there is little power to detect an age effect using age-matched controls, though the direction of effect is similar.
Using
interaction tests, there was no suggestion that there were BMI effects in younger or older mothers (data not shown).
COMMENTS
Our results confirm the previously reported association between low maternal age and gastroschisis but suggest that within our UK population the apparent link between low BMI and gastroschisis reported elsewhere is because younger mothers are thinner, rather than because of a direct effect.
Using a case control method allowed us to investigate a rare condition but the retrospective nature of our data collection means that other confounding factors such as smoking history, recreational drug use or medications and medical history may not be included.
A possible weakness or our study is
that mothers with affected fetuses were referred to the Princess Anne Hospital from hospitals across the Wessex health region, whereas all controls were taken from deliveries within the tertiary unit. However there are not great differences in the age structure, ethnicity or social class of women booked at different hospitals in Wessex so it is unlikely this would materially affect our results.
Our study used measured height and weight at pregnancy booking to calculate BMI. This differs from some papers[3] that use self-reported weight to estimate pre-pregnancy BMI. We believe that using measured weight is likely to be more accurate, because the measurements were taken in early pregnancy they were likely to be little-changed from before pregnancy, and that any change there was is likely to be consistent across all study groups.
American studies have found lower BMI to be associated with a higher risk of gastroschisis[3-4], after controlling for multiple confounders including age, in case groups of 464 and 104 infants respectively, although the larger study does note that the increased risk associated with low age is not offset by an increased bodyweight until very high BMIs are reached. One implication of this observation is that there may be some relationship to biological immaturity in the pregnancy state that may lead to development of this birth defect, as opposed to a lower BMI being simply a proxy of under nutrition[3-4].
Paranjothi et al[10] also investigated the link between maternal nutrition and gastroschisis in a UK population comparing mothers with affected fetuses with age-matched controls.
Like Siega-Riz et al[3] and Lam et al[4] they
found BMI was associated with a lower risk of gastroschisis only when the mother was obese (BMI > 30kg/m2). Thus the greatest influence on risk of gastroschisis appears to be low maternal age. Further studies are needed to investigate how these are linked.
ACKNOWLEDGEMENTS
We would like to thank Sally Boxall Nurse Specialist in Wessex Fetal Medicine Department for help with access to the WANDA Database.
DISCLOSURE
To my knowledge there are no competing interests and no individuals or companies that have financially contributed to this study.
References 1
Mastroiacovo P, Lisi A, Castilla EE. The incidence of gastroschisis: Research urgently needs resources. BMJ 2006;332:423–424 2
Stevenson RE, Rogers RC, Chandler JC, Gauderer MWL, Hunter AGW. Escape of the yolk sac: a hypothesis to explain the embryogenesis of gastroschisis. Clin Genet 2009;75:326–333 3
Siega-Riz AM, Herring AH, Olshan AF, Smith J, Moore C. The joint effects of maternal prepregnancy body mass index and age on the risk of gastroschisis. Paediatric and perinatal epidemiology 2008;23:51-57. 4
Lam PK, Torfs CP, Brand RJ. A low pre-pregnancy body mass index is a risk factor for an offspring with gastroschisis Epidemiology 1999;10:717-721. 5
Torfs CP, Katz EA, Bateson TF, Lam PK, Curry CJR. Maternal medications and environmental exposures as risk factors for gastroschisis. Teratology 1996;54:84–92. 6
Kozer E, Nikfar S, Costei A, Boskovic R, Nulman I, Koren G. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: A meta-analysis. Am J Obstet and Gynaecol 2002;187:6:1623-1630. 7
Torfs CP, Velie EM, Oechsli FW, Bateson TF, Curry CJR. A populationbased study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 1994;50:44–53. 8
Drongowski RA, Smith RK, Coran AG, Klein MD. Contribution of demographic and environmental factors to the etiology of gastroschisis: a hypothesis. Fetal Diagn Ther 1991; 6:14–27 9
Torfs CP, Christianson RE, Lovannisci DM, Shaw GM, Lammer EJ. Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis. Birth defects research (Part A): Clinical and Molecular Teratology 2006;76:723-730 10
Paranjothy S, Broughton H, Evans A, Huddart S, Drayton M, Jefferson R, Rankin J, Draper E, Cameron A, Palmer SR. The role of maternal nutrition in the aetiology of gastroschisis: an incident case-control study. International Journal of Epidemiology 2012; 41:1141-1152
Table 1 – Distribution of cases and controls by Age, BMI and Parity
Cases Mother’s Age (Years) <19 20-24 25-29 30-34 35+ Total Mean S.D. Min Age Max Age Mother’s BMI (kg/m2) <20 20-22.5 22.5-25 25-30 30+ Total Mean S.D. Min BMI Max BMI Parity Pregnancy Number 1 2 3+ All
% (n)
Next Delivery Controls % (n)
Age-Match Controls % (n)
37.4 (43) 38.3 (44) 15.7 (18) 5.2 (6) 3.5 (4) 100 (115) 22.1 5.0 14.7 40.0
9.6 (11) 20.9 (24) 23.5 (27) 32.2 (37) 13.9 (16) 100 (115) 28.8 6.1 16.8 41.7
38.3 (44) 37.4 (43) 16.5 (19) 4.3 (5) 3.5 (4) 100 (115) 22.2 5.0 14.8 40.0
% (n)
% (n)
% (n)
11.3 (13) 20.0 (23) 33.9 (39) 24.3 (28) 10.4 (12) 100 (115) 24.4 3.9 16.7 36.8
7.8 (9) 24.3 (28) 24.3 (28) 21.7 (25) 21.7 (25) 100 (115) 25.8 5.6 16.5 47.6
16.7 (19) 21.9 (25) 27.2 (31) 20.2 (23) 14.0 (16) 100 (114) 24.7 5.2 16.9 42.9
% (n)
% (n)
% (n)
64 (74) 21 (24) 15 (17) 100 (115)
40 (46) 22 (25) 38 (44) 100 (115)
57 (65) 26 (30) 17 (20) 100 (115)
Table 2 - Odds ratio for gastroschisis according to age, body mass index (BMI) and control type.
Model
All Control Pool 1 2 3
Next Delivery Controls 4 5 6
Age Match Controls 7 8 9
Predictor
Odds Ratio (OR)
95% Confidence Intervals
P value
Age (In Years) BMI (In kg/m2) Age (In Years) BMI (In kg/m2)
0.02 0.45 0.02 0.84
0.004-0.11 0.13-1.56 0.004-0.12 0.22-3.28
<0.001 0.21 <0.001 0.80
Age (In Years) BMI (In kg/m2) Age (In Years) BMI (In kg/m2)
0.007 0.24 0.008 0.81
0.001-0.004 0.05-1.05 0.001-0.04 0.12-5.69
<0.001 0.06 <0.001 0.83
Age (In Years) BMI (In kg/m2) Age (In Years) BMI (In kg/m2)
0.02 0.85 0.02 0.84
0.000-281 0.19-3.77 0.000-295 0.19-3.76
0.41 0.83 0.41 0.82