IJE Advance Access published online on June 7, 2008
International Journal of Epidemiology, doi:10.1093/ije/dyn100
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Caesarean section among relatives
1Department of Public Health and Primary Health Care, Section for Epidemiology and Medical Statistics, University of Bergen, Norway.
2Medical Birth Registry of Norway, Locus of Registry Based Epidemiology, University of Bergen, Norway.
3Norwegian Institute of Public Health, Oslo, Norway
4Department of Obstetrics and Gynaecology, Haukeland University Hospital, University of Bergen, Norway.
*Corresponding author. Department of Public Health and Primary Health Care, University of Bergen, Postboks 7804, N-5020 Bergen, Norway. E-mail: mette.tollanes{at}isf.uib.no.
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Abstract |
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Background Caesarean section rates are increasing. It is not clear whether a familial predisposition to caesarean section exists.
Methods Births registered in the Medical Birth Registry of Norway during 1967–2005 were linked to construct 440 236 grandmother–parent units and 275 001 same sex full sibling units. Log-binomial regression models were used to explore associations.
Results A mother born by caesarean section had a 55% increased risk of having her first child by caesarean section [adjusted relative risk (RR) 1.55, 95% CI 1.48–1.62]. The same was not found for fathers born by caesarean section (RR 1.02, 95% CI 0.96–1.10). A younger sister, whose older sister had her first child by caesarean section, had a 45% increased risk of having her first child by caesarean section (RR 1.45, 95% CI 1.40–1.51). If an older brother had his first child by caesarean, this did not constitute an increased risk for the younger brother's partner (RR 1.02, 95% CI 0.97–1.08). Similar associations were found in the subgroups of obstetric low risk deliveries.
Conclusions A female-to-female familial predisposition to caesarean section was observed. It could be caused by biologic inheritance, primarily working through maternal alleles and/or environmental factors. The results imply that both mechanisms could be important.
Keywords Familial predisposition, caesarean section, biologic inheritance, environmental factors
Accepted 7 May 2008
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Introduction |
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Caesarean section rates are increasing world-wide, in Norway from 2.0% in 1968 to 16.4% in 2006.1 The reasons for the increase are to a large degree unclear; it cannot simply be attributed to increased obstetric risk.2 When medically indicated, caesarean section can undoubtedly save lives and reduce morbidity. However, caesarean section is also associated with both short- and long-term adverse outcomes in mother and child3,4 and represents an economic burden to society.5 The reasons for the increase are, therefore, of importance to investigate further.
In recent years, several studies have focused on the occurrence of familial aggregation of pregnancy complications and adverse outcomes, some of which may serve as indications for caesarean section. For instance, an excess recurrence in families has been observed of pre-eclampsia,6–10 prolonged pregnancy,11 preterm birth,12,13 reduced intrauterine growth,13–15 birth defects16–18 and dystocia,19,20 as well as correlations of birth weight21 and gestational age21,22 across generations. Also, familial recurrence exists of factors like maternal height23 and body mass index.24 Since both pregnancy complications and maternal factors are associated with caesarean section rates, it seems reasonable to hypothesize that caesarean section may recur in families. However, to our knowledge, only one study, based on a small set of data, has investigated and found a familial predisposition to operative delivery, in which a family history of caesarean section represented an 
40% increased risk of caesarean section.25
The aim of the present study, using data from the population-based Medical Birth Registry of Norway (MBRN), was to explore familial predispositions to delivery by caesarean section, both across and within generations.
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Methods |
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Since 1967, all live and stillbirths from 16 weeks of gestation in Norway have been notified to the MBRN based on compulsory notification.26 The registry comprises demographical data of the parents and child, including the national identification number of both parents, maternal health before and during pregnancy, complications and interventions during pregnancy and delivery, as well as the condition of the newborn. Data are transferred by the midwives to the notification form the hospital record and the pregnancy record, which the woman brings to the delivery unit. Data on complications and maternal disease have been entered into the notification form verbatim until 1998 and in checkboxes or verbatim from 1999 onwards. The notification form is sent to the MBRN within the ninth day postpartum or at discharge from the delivery or neonatal care unit. Verbatim data on maternal disease have been coded according to International Classification of Disease (ICD)-8 during 1967–98 and ICD-10 from 1999 onwards. Verbatim data on complications have been coded according to a system for the MBRN based on international definitions during 1967–98 and according to ICD-10 from 1999 onwards. Great efforts have been made by the medical and technical staff at the MBRN to ensure that the categories are comparable between the two versions of ICD.
All live births are also notified in a parallel civil system to Statistics Norway, where the national identification number of the newborn is generated and a record established in the Central Population Registry. All records of the MBRN and the Central Population Registry are matched, to ensure medical notification of every newborn in the country.26 Data on births thus discovered to be missing from the MBRN (80–100 each year) are then collected from the delivery units.27
From 1967 through 2005, 2 216 949 singleton births were registered. By internal record linkage using the national identification number, 261 156 parturients were identified with a female newborn who became a mother later in life. These parturients and their births were linked to grandmother–mother units. We examined only the first birth of each mother, but allowed the mother herself to be of any birth order. Similarly, 179 080 parturients were identified with a male newborn who became a father later in life, and linked to grandmother–father units. We also used the national identification number to link 153 085 pairs of full sisters and 121 916 pairs of full brothers with their first births. We used only the oldest same sex sibling unit of each sibship, meaning each sister or brother occurred only in one unit.
We constructed low risk subgroups of grandmother–parent units by excluding grandmothers and mothers with a record of pre-eclampsia, pre-gestational diabetes, breech delivery, abruptio placentae, placenta previa or dystocia, as well as units where either mother/father or offspring had a birth weight below 2500 or above 4500 g or a gestational age below 37 or above 42 weeks. The subgroups thus included 96 953 low risk grandmother–mother units and 63 339 low risk grandmother–father units. We also constructed subgroups of low risk full-sibling units, using the same criteria as for grandmother–parent units, leaving 53 336 low risk full sister units and 42 323 low risk full brother units for analyses.
The statistical analyses were carried out in STATA version 9.2, where log-binomial regression models were used to obtain relative risks (RRs) as effect measures. In grandmother–parent units, the exposure was the grandmother delivering the parent by caesarean section, and the outcome was whether or not the parent's first child (offspring) was born by caesarean section. In full sibling units, the exposure was whether the older sibling's first child was delivered by caesarean section, and the outcome was whether the younger sibling had its first child by caesarean section.
Time and maternal age were considered potential confounders, as the caesarean section rates have increased steadily since 1967 and the risk of caesarean section increases with age;28 family members may tend to have children at similar ages. The grandmother–parent analyses were thus adjusted for the categorical variables year of birth of the offspring (1980–89, 1990–94, 1995–99, 2000–05), and age of the offspring's mother (<25, 25–34, 35+). The full sibling analyses were adjusted for year of birth of the younger sibling's child (1967–76, 1977–86, 1987–96, 1997–2005) and the age of its mother (<25, 25–34, 35+). However, adjustments did not considerably alter the effect measures. We also checked for interactions between the exposure and each of the confounders, but none were found. Two-sided P-values below 0.05 were considered statistically significant.
We confirm that research ethics committees in Norway regularly exempt research on anonymous registry data from ethical review.
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Results |
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Among the mothers and fathers born during 1967–71, 1.7 and 1.9% were born by caesarean section, respectively (Table 1). For mother and fathers born during 1982–90, the rates increased to 8.2 and 9.2%. Among older sisters, 3.1% had their first child by caesarean section during 1967–76, against 16.5% during 1997–2005. The majority of younger siblings had their first child in the same period as their older sibling or the subsequent period (80% of sisters and 78% of brothers).
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A mother born by caesarean section had an increased risk of having her first child by caesarean compared with a mother born vaginally (Figure 1, panel A), overall, a 55% increased risk (adjusted RR 1.55, 95% CI: 1.48–1.62, Table 2). If a mother was born by caesarean section after a low risk pregnancy, and her own pregnancy was uncomplicated, she had twice the risk of having her first child by caesarean section (adjusted RR 2.06, 95% CI: 1.69–2.50).
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The same association was not found for fathers born by caesarean section (Figure 1, panel B). Their partners showed no increased risk of having their first child by caesarean section, compared with partners of fathers born vaginally (adjusted RR 1.02, 95% CI: 0.96–1.10, Table 2).
Limiting the analyses to the grandmother–parent units where the parents themselves were also first born did not alter the results (data not shown).
A younger sister whose older sister had her first child by caesarean section had an increased risk of having her first child by caesarean section, compared with a younger sister of an older sisters who had her first child vaginally (Figure 2, panel A). Overall, she had a 45% increased risk (adjusted RR 1.45, 95% CI: 1.40–1.51, Table 3). If both sisters were healthy and had uncomplicated pregnancies, the overall excess risk was similar (adjusted RR 1.53, 95% CI: 1.27–1.86).
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Such an association was not found for brothers. If an older brother had his first child by caesarean section, the risk of caesarean section for the younger brother's partner was not increased (Figure 2, panel B).
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Discussion |
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We found both inter- and intra-generational predispositions to caesarean section. A mother born by caesarean section was more likely to have her first child by caesarean section. Likewise, a pregnant woman whose older sister had a caesarean section, had an increased risk of having a caesarean section herself. Similar associations were found in obstetric low risk subgroups. However, a father born by caesarean section had no increased risk of having his first child by caesarean section, nor did caesarean section in older brothers’ partners influence the risk of caesarean section in the younger brothers’ partners.
Important strengths of our study include the large, population-based study cohort. The completeness of the MBRN26,27 assures a negligible risk of selection bias. Exposures and outcomes were reported separately at different times. This ensures any information bias caused by misclassification will be non-differential. Several of the variables in the MBRN have been validated and found to be satisfactory,29–32 indicating reliable data.
One weakness of our study is the lack of data on some possibly important confounders. In particular, lack of data on maternal height and weight could represent a limitation. High body mass index is associated with an increased risk of caesarean section,33,34 and recurs in families.24 Also, other medical/biological conditions that run in families and predispose to caesarean section could exist without being registered, confounding our results.
Social status is another possible confounder on which we had no data. However, a recent study showed that social class, measured in maternal level of education, was not a strong predictor of caesarean section in Norway.35 Thus, we do not believe social status to be an important confounder.
Since conditions that serve as indications for caesarean section run in families, the familial aggregation found in this study was expected. Examples of such conditions are pre-eclampsia,6–10 prolonged pregnancy,11 reduced intrauterine growth,13–15 dystocia19,20 and preterm birth.12,13 Varner et al.25 found an intergenerational predisposition to operative delivery. A mother born by caesarean section had a 40% increased risk (odds ratio 1.4, 95% CI: 1.2–1.7) of delivering by caesarean herself, which is consistent with our results.
Two mechanisms could possibly contribute to the observed familial aggregation of caesarean section; firstly, biological inheritance through genes, and secondly, environmental or social influences, through habits and learning.
Different types of genetic inheritance could cause predisposition to caesarean section.36 If the condition leading to caesarean section is inherited through paternal alleles, it must operate through the foetus or the placenta. The mother provides the other half of the foetal genome, through which a predisposition to caesarean section may be inherited. In addition, a predisposition may be inherited through conditions related to the mother's ability to adapt to and carry a pregnancy, as well as completing labour, in which case the condition is inherited exclusively through maternal alleles passed from mother to daughter. A final possibility is inheritance through maternal mitochondria. Several indications for caesarean section have been reported to be inherited partly through paternal alleles, although in most cases to a larger degree through maternal alleles, for instance reduced intrauterine growth,14,15 pre-eclampsia6,9 and birth defects.18 However, our results derived from grandmother–father and full brother units, imply a negligible foeto-placental effect and any biologically inheritable predisposition to caesarean section is mainly acting through maternal alleles.
On the other hand, it is not unlikely that environmental or social factors (‘social inheritance’) could cause the observed patterns of association. A mother herself born by caesarean section could be raised learning this is the preferable way of giving birth. Many women who request a planned caesarean, believe it is safer for both mother and child.37 Such conceptions are likely to be passed on from mother to daughter and coexist between full sisters to a larger degree than between mother- and daughter-in-law or sisters-in-law.
We attempted to separate environmental factors from biological inheritance by creating subgroups of low risk units where no obvious indication for caesarean section was recorded in either woman. Again, there were negligible or no associations in grandmother–father and full brother units, while there were associations in grandmother–mother and full sister units comparable with the overall associations. This implies the existence of social inheritance. However, we cannot exclude that there are still biological factors that predispose to caesarean section, not registered in the MBRN, that are clustered within families in our low risk units, contributing to the observed pattern.
In healthy grandmother–mother and full sister units, there seemed to be a secular trend of an increasing absolute risk difference in caesarean section rates between exposed and unexposed over time. This could be consistent with the increasing use of caesarean section on more liberal indications, such as ‘maternal request’38 and supports the existence of a social inheritance of predisposition to caesarean section.
The effect of the exposure (mother being born by caesarean section) was apparently stronger in the low risk grandmother–mother units than in all units, adjusted RR 2.06 vs 1.55. This might be a consequence of the baseline risk being considerably lower in the low risk units, i.e. the doubling of a caesarean section rate, starting at a 4.6%, requires a smaller absolute increase than doubling the rate starting at 12.6%. Furthermore, in the full sister units, the adjusted RRs were similar in all units and low risk units. Births by sisters were in general closer in time, and, therefore, probably more comparable with regards to obstetric practice. Since the difference in effects between all and low risk units was not present among sisters, we do not believe the higher RR among low risk grandmother–mother units should be overly emphasized. Alternatively, the difference that appears in grandmother–mother units, but not in full sister units, can be interpreted as a stronger social inheritance from mother to daughter than between sisters.
In conclusion, we observed a female-to-female familial predisposition to caesarean section. An index woman's risk of caesarean section in her first birth was increased by 50% if her mother gave birth to her by caesarean section, or if an older sister had her first child by caesarean section. The same was not observed between grandmother and father or between full brothers. Both biological inheritance, primarily working through maternal alleles and environmental or social factors could explain this pattern. Our results imply that both mechanisms could be important, although quantifying further the contribution of each was not feasible in this study. Our findings may be relevant for personnel counselling women requesting a caesarean in the presence of no medical indication. A family history of caesareans might be a starting point for further reflection.
KEY MESSAGES
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The authors are grateful to Tone I Nordtveit for valuable comments on earlier versions of this manuscript. This study was supported by The Research Council of Norway.
Conflict of interest: None declared.
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References |
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