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
page: 25
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RESULTS
The case group consisted of 798 (3.49%) informative offspring while the control group included 1,624 (4.26%) newborns who had mothers with medically-recorded diagnosis of haemorrhoid in the prenatal maternity logbook. Of 798 case mothers, 276 (34.6%), while of 1,624 control mothers, 543 (33.4%) had haemorrhoid before the conception and during the study pregnancy. This condition was considered as chronic haemorrhoid, and about 90% of them occurred multiparae. In the rest, new-onset haemorrhoids started usually between the seventh and ninth gestational months.
The maternal demographic variables are shown in Table 1. Mean age of case and control mothers with haemorrhoid was 26.2 and 26.7 years, respectively. These figures are higher than the mean age (25.4 years) of control mothers without haemorroid. This difference is explained by the lower frequency in those 19 years or less of age and the higher frequency in those with 30 or more years of age. The mean birth order was 1.9 in pregnant women with haemorrhoid, higher in those without haemorrhoid (1.7-1.8). Haemorrhoid occurred more frequently in managerial (28.0% vs. 25.1%) and in mainly professional (17.2% vs. 10.2%) women. Folic acid and multivitamin supplementations were more frequent in women with haemorrhoid , both in case mothers (51.8% vs. 49.3%) and particularly in control mothers (57.1% vs. 54.3%). Nearly all other pregnancy supplements, except for vitamin D, were used more frequently by pregnant women with haemorrhoid.
Of 2,640 pregnant women visited at home, 101 (3.8%) recorder haemorrhoids, and 16 (18.8%) smoked during the study pregnancy. Of 2,539 pregnant women without haemorrhoids, 564 (22.2%) smoked. Of 800 control mothers visited at home, 36 (4.5%) had recorded haemorrhoids and 6 (16.7%) smoked, while of 764 pregnant women without haemorrhoids, 146 (19.1%) were smokers. About 1% of case and control mothers were hard or regular drinkers.
Among medically- recorded pregnancy complications in the maternity logbook, only the frequency of anaemia was significantly higher in both case mothers (23.8% vs. 13.8%, OR with 95% CI: 1.9, 1.6-2.3) and control mothers (24.4% vs. 16.3%, OR with 95% CI: 1.7, 1.5-1.9) with haemorrhoid compared to pregnant women without haemorrhoid.
The incidence of acute maternal diseases and the prevalence of chronic maternal disorders are shown in Table 2. All acute diseases, especially those of digestive system and due mainly to infectious diarrhoea, were more frequent in pregnant women with haemorrhoid. About 40% of those with haemorrhoid had a recorded diagnosis of constipation. Phlebitis-thrombophlebitis (11.3% vs. 1.7%), varicose veins of lower extremities (7.0% vs. 1.2%) and migraine (3.2% vs. 2.1%) showed a higher prevalence in pregnant women with haemorrhoid. Comparison of case and control mothers with haemorrhoid showed a significantly higher occurrence of influenza-common cold (36.8% vs. 27.5%), acute diseases of digestive system (10.0% vs. 6.0%) and constipation (45.7% vs. 39.3%) in case mothers than in control mothers with haemorrhoid.
We found no significant difference in the frequency of drugs used for the treatment of haemorrhoid in case and control mothers so we have combined them as 'pregnant women with or without haemorrhoid' (percentages are shown in parentheses). Treatment mainly consisted of tribenoside (Glyvenol®) (19.0% vs. 0.0%) and dobesylicum calcium (Doxium®) (4.7% vs. 0.0%) as tablet, phenol + bacterium coli (Reparon®) (18.2% vs. 0.3%), epinephrine + ephedrine + procaine + others (Hemorid®) (6.2% vs. 0.1%) as suppository and ointment, epinephrine + chloramphenicol + tetracaine + others (Nodicid®) (4.5% vs. 1.1%), lidocaine + others (Aurobin®) (8.1 vs. 0.2%) as ointments. However, the analgesic dipyrone (10.6% vs. 5.2%) and acetylsalicylic acid (7.7% vs. 4.0%), the antispasmodic drotaverine (12.7% vs. 8.8%), the laxative senna (6.5% vs. 2.0%) and the antifungal clotrimazole (12.1% vs. 7.6%) were also used more frequently by 2,422 pregnant women with haemorrhoid than by 58,572 pregnant women without haemorrhoid.
Only the birth outcomes of newborns without CA in the control group are shown Table 3, since CAs may have a more severe effect on gestational age at delivery and birth weight than haemorrhoid. There was no difference in sex ratio and in the mean gestational age between newborn infants born to pregnant women with or without haemorrhoid. However, the mean birth weight (3,339 vs. 3,273 g) was significantly larger in the newborns of mothers with haemorrhoid, but this 67 grams excess does not seem to be clinically important. The frequency of preterm births and of low birthweight was not significantly different in the newborns of mothers with or than in those of mothers without haemorrhoid.
The possible risk of maternal haemorrhoid for CAs in their offspring was estimated by comparing medically- recorded haemorrhoid in the mothers of cases with different CA groups (including at least 3 cases) and in those of their all matched controls (Table 4). There was no higher risk for the total group of CAs and for the multiple CA group, the upper limit of confidence interval not reaching 1. However, of the 22 groups of isolated CAs, exomphalos/gastroschisis was distinctive. Of the 238 cases, 172 had exomphalos/omphalocele and 66 had gastroschisis. (Umbilical hernia and exomphalos or gastroschisis as component of multiple CAs were excluded from this CA-group). Of 172 cases with isolated exomphalos, 14 (8.14%) had mothers with haemorrhoid during the study pregnancy (OR with 95% CI: 4.9, 1.7-7.9), while of 66 cases with gastroschisis, only one had a mother with haemorrhoid (1.52%; OR with 95% CI: 0.4, 0.1-1.2). After Bonferroni correction, the association of maternal haemorrhoid with a higher risk of exomphalos remained significant (p=0.03). The critical period for exomphalos is in the second and third gestational month, but of 14 cases with exomphalos, 13 had mothers with new-onset haemorrhoid that appeared after the third gestational month. All cases with exomphalos were diagnosed live-born infants and had no familial occurrence of this CA.
We also evaluated the different entities in the group of “Other isolated CAs”. Of these 868 cases, 31 had mothers with haemorrhoid, of which 8 cases had malposition/rotation of digestive organs, i.e., transposition of small intestine in 4 and malrotation of colon in 3. All were males and had no familial history of these CAs of gut. There were 53 (0.23%) cases with malposition/malrotation of gut in the total group of 22,843 CAs, of which 8 (1.00%) were born to 798 mothers with haemorrhoid (chi square: 17.8, p=0.0001). In addition, of the above 53 cases 8 (15.5%) had malposition/malrotation of gut, while of their 98 matched controls, 3 (3.1%) had mothers with haemorrhoid. This difference also shows a significant association with maternal haemorrhoid (OR with 95% CI: 17.2, 2.1-142.0, after Boferroni correction p=0.03). Of these 8 cases, 6 had mothers with chronic haemorrhoid.
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