Possible association of maternal haemorrhoid with congenital abnormalities in their children
– a population-based case-control study Ferenc Bánhidy, M.D.1, Nándor Ács, M.D.1, Erzsébet H. Puhó2, and Andrew E. Czeizel2* *Corresponding Author: Andrew E. Czeizel, Foundation for the Community Control of Hereditary Diseases, 1026 Budapest, Törökvész lejtõ 32. Hungary; Tel: +36 1 3944 712, Fax: +36 1 3944 712; E-mail: czeizel@interware.hu
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DISCUSSION
The above results made us reject the “no association” hypothesis because of the higher risk of exomphalos and malposition-malrotation of gut in children of mothers with haemorrhoid during pregnancy.
We confirmed that pregnant women with haemorrhoid are older and comprise a higher proportion of multiparae [3]. About two-thirds of pregnant women had new-onset haemorrhoid during the study pregnancy, suggesting that pregnancy itself (not only delivery) is a predisposing factor for haemorrhoid. Haemorrhoid was more frequent in women with higher socioeconomic status and healthier lifestyle (who had a lower proportion of smokers), and higher standard of prenatal care including more frequent folic acid/multivitamin supplementation. These factors may explain a somewhat larger mean birth weight in children born to such mothers.
Anaemia is a common complication of haemorrhoid because of the frequently associated bleeding. Acute diseases of digestive system (mainly diarrhoea) and constipation were also more frequently associated with haemorrhoid. The more frequent phlebitis-thrombophlebitis, varicose veins of the lower limbs and migraine may be explained partly by advanced maternal age, but may also have some common genetic and/or environmental background with haemorrhoid.
Two important characteristics of pregnant women with haemorrhoid in this study were that the diagnosis of haemorrhoid was based on medically- recorded data in the maternity logbook and that most pregnant women were treated with drugs indicating the severity of their condition.
Our major finding was the possible association of maternal haemorrhoid with exomphalos and malposition/malrotation of gut in their newborn infants. The question is whether these possible associations are connected with the effect of maternal haemorrhoid itself, the causes of haemorrhoid, related drug treatments or other confounders and chance effect .
Exomphalos (or omphalocele) is a pathologically expanded umbilical hernia in which fetal liver and frequently bowel extrude (sometimes with malrotation of intestines), covered by a membrane which may or may not remain intact prior to, during or after delivery [13]. Approximately 25-40% of infants with exomphalos have other CAs and most of these multimalformed cases involve abnormal karyotypes or may be the component of other CA-syndromes with Mendelenian origin such as Beckwith-Wiedemann syndrome [14]. However, multiple CAs including exomphalos and umbilical hernia were excluded from our cases of exomphalos. The prevalence of isolated exomphalos was 0.2 per 1000 births in Hungary [15], and sometimes exhibited familial clustering [16-18].
An important argument against a causal association of the exomphalos in our cases with maternal haemorrhoid being an environmental factor is that all but one such case occurred in pregnant women with new-onset haemorrhoid, i.e. after the critical period of this CA, between the 6th and 11th gestational weeks.
Malposition/malrotation of gut occured more frequently in newborns of mothers with haemorrhoid. Atresia and stenosis of pylorus, small and large intestines, rectum/anal canal are well-known CAs of gut, but malposition/malrotation of gut is much less-known [3]. The mechanism of these CAs was described as a failure of the bowel to undergo normal migration and attachment on returns from physiological omphalocele to the celomic cavity and to simultaneously rotate in a counter clockwise direction around the superior mesenteric pedicle. Eventually the caecum and right colon become fixed to the posterior abdominal wall by the Toldt fusion fascia. If the rotation does not proceed to completion, fixation of the right colon does not occur and the entire intestine will have a narrowed pedicle. These defects may follow arrest of development during the 12th and 13th gestational week. However, reports regarding the etiology of transposition/malrotation of stomach, small intestine, colon are very limited but may be autosomal dominantly inherited CA [19, 20]. None of our cases were familial.
The relationship of exomphalos and malposition/malrotation of gut suggests a possible causal association with maternal haemorrhoid, because this “triad” may have a common genetic background and this hypothesis merits further study.
The drugs used in treatment of our pregnant women showed no causal association with haemorrhoid. This agrees with the scarce data on these drugs [2, 21]. Supplementary drugs such as drotaverine [22], dipyrone [23], acetylsalicylic acid [24, 25], senna [26] and clotrimazole [27] also do not increase risk for CAs.
The value of folic acid/multivitamin supplementation in prevention of exomphalos is debatable [28, 29], nevertheless, folic acid supplementation as confounder was evaluated in the study, because mothers with hemorrhoid used folic acid more frequently in the early pregnancy as well.
When a large number of statistical tests are performed, a significant difference (p<0.05) is expected in every 20th calculation by chance alone. However, associations found in the study remained significant after the Bonferroni adjustment [12].
Since only women with severe, treated medically-recorded haemorrhoid were evaluated in our study, we cannot extrapolate the findings to mild haemorrhoid. Recent studies have shown an association of maternal obesity with exomphalos [29-31], but prepregnancy body mass index (BMI) of our pregnant women was not known.
In conclusion, we found a higher risk for exomphalos and malposition-malrotation of gut in the offspring of pregnant women with haemorrhoid. Further studies are needed to check these possible associations with the maternal haemorrhoid.
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