Hagman A, Källén K, Bryman I, Landin-Wilhelmsen K, Barrenäs ML, Wennerholm UB. Morbidity and Mortality after Childbirth in Women with Turner Karyotype

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Geburten, Morbidität, Mortalität Hagman A, Källén K, Bryman I, Landin-Wilhelmsen K, Barrenäs ML, Wennerholm UB Morbidity and Mortality after Childbirth in Women with Turner Karyotype Hum Reprod 2013;

diese mit der Morbidität und Mortalität von gesunden Frauen () und Ullrich-Turner-Frauen ohne Geburt (n=378).

1 Geburten, Morbidität, Mortalität Hagman A, Källén K, Bryman I, Landin-Wilhelmsen K, Barrenäs ML, Wennerholm UB Morbidity and Mortality after Childbirth in Women with Turner Karyotype Hum Reprod 2013; 28 (7): Diese Studie untersuchte retrospektiv die Mortalität und Morbidität nach der Geburt anhand des schwedischen Geburtsregisters bei 124 Frauen mit Ullrich-Turner-Syndrom und verglich diese mit der Morbidität und Mortalität von gesunden Frauen () und Ullrich-Turner-Frauen ohne Geburt (n=378). Bei Ullrich- Turner-Frauen, welche ein Kind gebaren, war keine erhöhte Mortalität zu verzeichnen. Kardiovaskuläre Erkrankungen traten bei Frauen mit Ullrich-Turner-Syndrom unterhalb 40 Jahren signifikant häufiger auf als bei gesunden Frauen (Haz ard Ratio [HR] 4,59; 95 % CI 2,75 7,66), jedoch nicht häufiger bei Frauen > 40 Jahren (Tab. 1 & 2), während sich andere Erkrankungshäufigkeiten nicht unterschieden. Die Morbidität durch kardiovaskuläre Erkrankungen war vor (HR 3,83; 95 % CI 1,02 14,43) und während der Schwangerschaft bei Ullrich-Turner-Frauen erhöht (HR 5,78; 95 % CI 1,94 17,24), nicht jedoch nach der Geburt (Tab. 4). Ein Aortenaneurysma wurde bei 11 der 502 (2,2 %) aller untersuchten Frauen mit Turner-Karyotyp beobachtet. Bei drei weiteren Frauen mit Turner-Karyotyp (2,4 %) fand sich ein Aortenaneurysma während der Schwangerschaft. Die Langzeitbeobachtung zeigte, dass die häufigste Todesursache bei Ullrich-Turner-Frauen eine Aortendissektion war, unabhängig davon, ob ein Kind geboren wurde oder nicht. Das Krebsrisiko war bei Frauen mit Ullrich-Turner-Syndrom nicht erhöht. Da eine Aortendissektion die häufigste Todesursache bei Ullrich-Turner-Frauen im gebärfähigen Alter ist und diese bevorzugt bei kardialen Fehlbildungen oder Bluthochdruck auftritt (Hewitt 2013), sollte vor einer Schwangerschaft das kardiovaskuläre System genau untersucht werden und bei Risikofaktoren von einer Schwangerschaft eher abgeraten werden.

2 Morbidity by age at first diagnosis Women with Turner karyotype MBR control group With childbirth, Without childbirth, n=378 Total, n=502 With childbirth, n=80 n=378 n=104 n=502 n=184 n=800 circulatory system, all 14 (11.3) 1 (1.2) 34 (9.0) 6 (5.8) 48 (9.6) 7 (3.8) 26 (2.1) 22 (2.8) Hypertension 0 (0.0) 1 (1.2) 11 (2.9) 2 (1.9) 11 (2.2) 3 (1.6) 7 (0.6) 11 (1.4) Ischaemic heart disease 0 (0.0) 0 (0.0) 2 (0.5) 1 (1.0) 2 (0.4) 1 (0.5) 1 (0.1) 1 (0.1) Valvular disease 5 (4.0) 0 (0.0) 7 (1.9) 1 (1.0) 12 (2.4) 1 (0.5) 1 (0.1) 1 (0.1) Arrhythmia 2 (1.6) 1 (1.2) 5 (1.3) 0 (0.0) 7 (1.4) 1 (0.5) 5 (0.4) 3 (0.4) Aortic aneurysm 3 (2.4) 0 (0.0) 8 (2.1) 0 (0.0) 11 (2.2) 0 (0.0) 0 (0.0) 0 (0.0) Cerebrovascular disease 2 (1.6) 0 (0.0) 3 (0.8) 2 (1.9) 5 (1.0) 2 (1.1) 2 (0.2) 2 (0.2) Thromboembolic diseases (incl. pulmonary embolism) 1 (0.8) 0 (0.0) 1 (0.3) 1 (1.0) 2 (0.4) 1 (0.5) 4 (0.3) 1 (0.1) Cardiac malformations, all 4 (3.2) 0 (0.0) 19 (5.0) 1 (1.0) 23 (4.6) 1 (0.5) 3 (0.2) 0 (0.0) Bicuspid aortic valve 1 (0.8) 0 (0.0) 9 (2.4) 0 (0.0) 10 (2.0) 0 (0.0) 0 (0.0) 0 (0.0) Aortic coarctation 1 (0.8) 0 (0.0) 12 (3.2) 0 (0.0) 13 (2.6) 0 (0.0) 0 (0.0) 0 (0.0) Renal malformations, all 1 (0.8) 0 (0.0) 6 (1.6) 0 (0.0) 7 (1.4) 0 (0.0) 0 (0.0) 0 (0.0) metabolic, diseases, all 23 (18.5) 3 (3.8) 80 (21.2) 2 (1.9) 103 (20.5) 5 (2.7) 48 (3.9) 21 (2.6) Diabetes mellitus 0 (0.0) 0 (0.0) 10 (2.6) 0 (0.0) 10 (2.0) 0 (0.0) 5 (0.4) 2 (0.2) Thyroid diseases, all 15 (12.2) 2 (2.5) 27 (7.1) 1 (1.0) 42 (8.4) 3 (1.6) 17 (1.4) 12 (1.5) Hypothyreosis 13 (10.6) 2 (2.5) 18 (4.7) 0 (0.0) 31 (6.2) 2 (1.1) 12 (1.0) 11 (1.4) Thyreotoxicosis 2 (1.6) 0 (0.0) 2 (0.5) 1 (1.0) 4 (0.8) 1 (0.5) 4 (0.3) 1 (0.1) Thyroiditis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Gastrointestinal diseases, all 19 (15.4) 0 (0.0) 51 (13.5) 3 (2.9) 70 (13.9) 3 (1.6) 103 (8.4) 23 (2.9) liver 2 (1.6) 0 (0.0) 2 (0.5) 0 (0.0) 4 (0.8) 0 (0.0) 4 (0.3) 2 (0.2) Diseases of gallbladder and pancreas Crohn s disease and ulcerative colitis 8 (6.5) 2 (2.5) 4 (1.1) 1 (1.0) 12 (2.4) 3 (1.6) 35 (2.8) 12 (1.5) 2 (1.6) 0 (0.0) 6 (1.6) 0 (0.0) 8 (1.6) 0 (0.0) 5 (0.4) 1 (0.1) Epilepsy 2 (1.6) 0 (0.0) 6 (1.6) 0 (0.0) 8 (1.6) 0 (0.0) 7 (0.6) 1 (0.1) Osteoporosis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Morbidity by age at first diagnosis in women with Turner karyotype and controls a Tabelle 1 mod. nach Hagman A et al Data from the NPR and the CDR. a a woman can have more than one diagnosis. MBR: Medical Birth Register; NPR: National Patient Register; CDR: Swedish Cause of Death Register

3 Women with Turner karyotype and childbirth versus women with Tuner karyotype without childbirth Women with Turner karyotype (with or without childbirth) versus MBR control group (with childbirth) Total HR (95% CI) Total HR (95% CI) metabolic diseases, all 1.02 ( ) 0.21 ( ) 0.77 ( ) 4.59 ( ) 1.48 ( ) 3.31 ( ) 1.54 ( ) 1.60 ( ) 3.44 ( ) 1.09 ( ) 2.73 ( ) Thyroid diseases, all 4.38 ( ) 4.08 ( ) 4.47 ( ) 1.11 ( ) 3.22 ( ) Gastrointestinal diseases, all 1.75 ( ) 1.52 ( ) 1.41 ( ) 0.59 ( ) 1.22 ( ) HRs for first diagnosis of four main groups by age at debut, presence of Turner karyotype and children Tabelle 2 mod. nach Hagman A et al Significant results (P < 0.05) in bold. The HRs were obtained using COX analyses, considering the time at risk for each woman, adjusting for women s year of birth. CI=Confidence Interval

4 Time of diagnosis in relation to Women with Turner karyotype MBR control group Before the first n=117 a Within 1 year of any delivery or more n=104 Before the first n=1160 c Within 1 year of any delivery 1-3 after the first 3 or more n= (4.3) 2 (1.6) 3 (2.4) 1 (0.8) 4 (3.8) 8 (0.7) 6 (0.5) 3 (0.2) 1 (0.1) 29 (2.8) Hypertension 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.0) 1 (1.0) 2 (0.2) 2 (0.2) 1 (0.1) 12 (1.2) Ischaemic heart disease 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.2) Valvular disease 2 (1.7) 0 (0.0) 1 (0.8) 1 (0.8) 1 (1.0) 0 (0.0) 1 (0.1) 0 (0.0) 0 (0.0) 1 (0.1) Arrhythmia 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 2 (1.9) 1 (0.1) 1 (0.1) 0 (0.0) 0 (0.0) 5 (0.5) Aortic aneurysm 0 (0.0) 2 (1.6) 1 (0.8) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Cerebrovascular disease 1 (0.8) 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 1 (0.1) 0 (0.0) 1 (0.1) 0 (0.0) 2 (0.2) Thromboembolic diseases (incl. pulmonary embolism) 1 (0.9) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.2) 1 (0.1) 0 (0.0) 0 (0.0) 2 (0.2) Cardiac malformations, all 0 (0.0) 2 (1.6) 2 (1.6) 0 (0.0) 0 (0.0) 1 (0.1) 2 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) Bicuspid aortic valve 0 (0.0) 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Aortic coarctation 0 (0.0) 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Renal malformations, all 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) metabolic, diseases, all 10 (8.6) 10 (8.1) 0 (0.0) 0 (0.0) 6 (5.8) 12 (1.0) 27 (2.2) 2 (0.2) 5 (0.4) 23 (2.2) Diabetes mellitus 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (0.3) 0 (0.0) 0 (0.0) 1 (0.1) 2 (0.2) Thyroid diseases, all 3 (2.6) 11 (8.9) 0 (0.0) 0 (0.0) 3 (2.9) 4 (0.3) 14 (1.1) 0 (0.0) 0 (0.0) 11 (1.1) Hypothyreosis 2 (1.7) 10 (8.1) 0 (0.0) 0 (0.0) 3 (2.9) 1 (0.1) 14 (1.1) 0 (0.0) 0 (0.0) 8 (0.8) Thyreotoxicosis 0 (0.0) 2 (1.6) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) 3 (0.3) Thyroiditis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Gastrointestinal diseases, all 7 (6.0) 3 (2.4) 1 (0.8) 3 (2.4) 5 (4.8) 54 (4.7) 8 (0.7) 13 (1.1) 5 (0.4) 46 (4.4) liver 1 (0.9) 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 2 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) 4 (0.4) Diseases of gallbladder and pancreas Crohn s disease and ulcerative colitis 2 (1.7) 0 (0.0) 1 (0.8) 2 (1.6) 5 (4.8) 10 (0.9) 1 (0.1) 10 (0.8) 2 (0.2) 24 (2.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (1.9) 5 (0.4) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.1) Epilepsy 0 (0.0) 2 (1.6) 0 (0.0) 0 (0.0) 0 (0.0) 4 (0.3) 2 (0.2) 1 (0.1) 0 (0.0) 1 (0.1) Osteoporosis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Morbidity in relation to in women with Turner karyotype and age- and parity-matched controls Tabelle 3 mod. nach Hagman A et al a Seven women had deliveries before b The time periods during any possible subsequent, and 1 year after each such, are not counted here. c 70 women had deliveries before 1987.

5 Women with Turner karyotype and childbirth versus MBR control group (with childbirth) Before the first or within 1 year after 1 or more after the first delivery Total metabolic diseases, all 3.83 ( ) 5.78 ( ) 1.91 ( ) 2.82 ( ) 4.26 ( ) 1.80 ( ) 3.37 ( ) Thyroid diseases, all 8.23 ( ) 2.68 ( ) 5.89 ( ) Gastrointestinal diseases, all 1.26 ( ) 2.08 ( ) 1.46 ( ) 1.63 ( ) HRs for the first diagnosis of four main groups by time in relation to in women with Turner karyotype compared with age- and parity-matched controls from the MBR Tabelle 4 mod. nach Hagman A et al Significant results (P < 0.05) in bold. The HRs were obtained using Cox analyses, considering the time at risk for each woman.

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