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result sql = Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy.
Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy.char = <;code = 60
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char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = A;code = 65
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 8;code = 56
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = d;code = 100
char = a;code = 97
char = y;code = 121
char = );code = 41
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = 7;code = 55
char = 6;code = 54
char = %;code = 37
char = ;code = 32
char = (;code = 40
char = 6;code = 54
char = 9;code = 57
char = /;code = 47
char = 9;code = 57
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 8;code = 56
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = y;code = 121
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = 7;code = 55
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = 8;code = 56
char = /;code = 47
char = 6;code = 54
char = 9;code = 57
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = ;code = 32
char = w;code = 119
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = I;code = 73
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = w;code = 119
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char = e;code = 101
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char = i;code = 105
char = m;code = 109
char = p;code = 112
char = r;code = 114
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char = e;code = 101
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result sql = OBJECTIVE : Apart from thalidomide, retinoids like isotretinoin are the strongest teratogens in humans known today. The overall risk of birth defects is estimated as up to 30% after exposure during embryogenesis. In spite of well established pregnancy prevention programs, pregnancies still occur during isotretinoin therapy in many countries including Germany. A detailed investigation of the incidence and outcome of these pregnancies would fill an important gap.
METHODOLOGY : The Berlin Institute for Clinical Teratology documents prospectively the course of drug-exposed pregnancies when contacted for individual drug risk assessment. Datasets of isotretinoin exposed pregnancies recorded between 1993 and 2008 were evaluated as to the outcome of pregnancy.
RESULTS : A total of 108 pregnancies exposed to systemic isotretinoin (median dosage 20 mg/day) during the contraindicated period were registered. 76% (69/91) of the pregnancies with known outcome were electively terminated-mainly for fear of medication risk. No terminations due to abnormal prenatal ultrasound findings were reported. Spontaneous abortions occurred in five pregnancies. Of 18 live births including 1 pair of twins 1 major birth defect (small ventricular septal defect) was observed. None of the infants showed symptoms of retinoid embryopathy. 70% (48/69) of the patients with data on contraception did not use any method, in 30% contraception failed. There was no evidence that poor maternal education was a major cause for the omission of contraception documented in 48 women.
CONCLUSION : Inadvertent isotretinoin exposure during the first 2 weeks post conception does not necessarily require discussion of termination of pregnancy, as the risk of major birth defects appears to be much lower than it becomes beyond this period. Nevertheless, additional efforts are required to improve the effectiveness of contraception while on isotretinoin treatment considering psycho-social aspects such as improved self-confidence, unexpected new partnership and sexual activity and incorrect perception of infertility.
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result sql = Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy.
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char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = G;code = 71
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = p;code = 112
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = M;code = 77
char = E;code = 69
char = T;code = 84
char = H;code = 72
char = O;code = 79
char = D;code = 68
char = O;code = 79
char = L;code = 76
char = O;code = 79
char = G;code = 71
char = Y;code = 89
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = e;code = 101
char = r;code = 114
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = T;code = 84
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = -;code = 45
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = u;code = 117
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = 9;code = 57
char = 9;code = 57
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 8;code = 56
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = A;code = 65
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 8;code = 56
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = d;code = 100
char = a;code = 97
char = y;code = 121
char = );code = 41
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = 7;code = 55
char = 6;code = 54
char = %;code = 37
char = ;code = 32
char = (;code = 40
char = 6;code = 54
char = 9;code = 57
char = /;code = 47
char = 9;code = 57
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 8;code = 56
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = y;code = 121
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = 7;code = 55
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = 8;code = 56
char = /;code = 47
char = 6;code = 54
char = 9;code = 57
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = ;code = 32
char = w;code = 119
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = I;code = 73
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = y;code = 121
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = s;code = 115
char = y;code = 121
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = -;code = 45
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = f;code = 102
char = -;code = 45
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = w;code = 119
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = h;code = 104
char = i;code = 105
char = p;code = 112
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = x;code = 120
char = u;code = 117
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
result sql = OBJECTIVE : Apart from thalidomide, retinoids like isotretinoin are the strongest teratogens in humans known today. The overall risk of birth defects is estimated as up to 30% after exposure during embryogenesis. In spite of well established pregnancy prevention programs, pregnancies still occur during isotretinoin therapy in many countries including Germany. A detailed investigation of the incidence and outcome of these pregnancies would fill an important gap.
METHODOLOGY : The Berlin Institute for Clinical Teratology documents prospectively the course of drug-exposed pregnancies when contacted for individual drug risk assessment. Datasets of isotretinoin exposed pregnancies recorded between 1993 and 2008 were evaluated as to the outcome of pregnancy.
RESULTS : A total of 108 pregnancies exposed to systemic isotretinoin (median dosage 20 mg/day) during the contraindicated period were registered. 76% (69/91) of the pregnancies with known outcome were electively terminated-mainly for fear of medication risk. No terminations due to abnormal prenatal ultrasound findings were reported. Spontaneous abortions occurred in five pregnancies. Of 18 live births including 1 pair of twins 1 major birth defect (small ventricular septal defect) was observed. None of the infants showed symptoms of retinoid embryopathy. 70% (48/69) of the patients with data on contraception did not use any method, in 30% contraception failed. There was no evidence that poor maternal education was a major cause for the omission of contraception documented in 48 women.
CONCLUSION : Inadvertent isotretinoin exposure during the first 2 weeks post conception does not necessarily require discussion of termination of pregnancy, as the risk of major birth defects appears to be much lower than it becomes beyond this period. Nevertheless, additional efforts are required to improve the effectiveness of contraception while on isotretinoin treatment considering psycho-social aspects such as improved self-confidence, unexpected new partnership and sexual activity and incorrect perception of infertility.
Publication: Arch. Gynecol. Obstet. 2010 Feb ;281(2)::221-7. :doi: 10.1007/s00404-009-1112-2.
Publication Date: 2010 Feb
Study Author(s): Schaefer, Christof;Meister, Reinhard;Weber-Schoendorfer, Corinna;
Institution: Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (BBGes), Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Spandauer Damm 130, Haus 10, 14050, Berlin, Germany. [email protected]
Shortcut link to this study:
Publication Date: 2010 Feb
Study Author(s): Schaefer, Christof;Meister, Reinhard;Weber-Schoendorfer, Corinna;
Institution: Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (BBGes), Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Spandauer Damm 130, Haus 10, 14050, Berlin, Germany. [email protected]
Shortcut link to this study:
OBJECTIVE : Apart from thalidomide, retinoids like isotretinoin are the strongest teratogens in humans known today. The overall risk of birth defects is estimated as up to 30% after exposure during embryogenesis. In spite of well established pregnancy prevention programs, pregnancies still occur during isotretinoin therapy in many countries including Germany. A detailed investigation of the incidence and outcome of these pregnancies would fill an important gap.
METHODOLOGY : The Berlin Institute for Clinical Teratology documents prospectively the course of drug-exposed pregnancies when contacted for individual drug risk assessment. Datasets of isotretinoin exposed pregnancies recorded between 1993 and 2008 were evaluated as to the outcome of pregnancy.
RESULTS : A total of 108 pregnancies exposed to systemic isotretinoin (median dosage 20 mg/day) during the contraindicated period were registered. 76% (69/91) of the pregnancies with known outcome were electively terminated-mainly for fear of medication risk. No terminations due to abnormal prenatal ultrasound findings were reported. Spontaneous abortions occurred in five pregnancies. Of 18 live births including 1 pair of twins 1 major birth defect (small ventricular septal defect) was observed. None of the infants showed symptoms of retinoid embryopathy. 70% (48/69) of the patients with data on contraception did not use any method, in 30% contraception failed. There was no evidence that poor maternal education was a major cause for the omission of contraception documented in 48 women.
CONCLUSION : Inadvertent isotretinoin exposure during the first 2 weeks post conception does not necessarily require discussion of termination of pregnancy, as the risk of major birth defects appears to be much lower than it becomes beyond this period. Nevertheless, additional efforts are required to improve the effectiveness of contraception while on isotretinoin treatment considering psycho-social aspects such as improved self-confidence, unexpected new partnership and sexual activity and incorrect perception of infertility.
METHODOLOGY : The Berlin Institute for Clinical Teratology documents prospectively the course of drug-exposed pregnancies when contacted for individual drug risk assessment. Datasets of isotretinoin exposed pregnancies recorded between 1993 and 2008 were evaluated as to the outcome of pregnancy.
RESULTS : A total of 108 pregnancies exposed to systemic isotretinoin (median dosage 20 mg/day) during the contraindicated period were registered. 76% (69/91) of the pregnancies with known outcome were electively terminated-mainly for fear of medication risk. No terminations due to abnormal prenatal ultrasound findings were reported. Spontaneous abortions occurred in five pregnancies. Of 18 live births including 1 pair of twins 1 major birth defect (small ventricular septal defect) was observed. None of the infants showed symptoms of retinoid embryopathy. 70% (48/69) of the patients with data on contraception did not use any method, in 30% contraception failed. There was no evidence that poor maternal education was a major cause for the omission of contraception documented in 48 women.
CONCLUSION : Inadvertent isotretinoin exposure during the first 2 weeks post conception does not necessarily require discussion of termination of pregnancy, as the risk of major birth defects appears to be much lower than it becomes beyond this period. Nevertheless, additional efforts are required to improve the effectiveness of contraception while on isotretinoin treatment considering psycho-social aspects such as improved self-confidence, unexpected new partnership and sexual activity and incorrect perception of infertility.
PMID: 19444462
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