Drugs during pregnancy
Drugs during pregnancy
1 Introduction. 1
2 The Alert Clinician”. 3
2.1 Thalidomide. 4
2.2 Anticonvulsants. 4
2.3 Warfarin. 5
2.4 Drugs for Thyrotoxicosis. 5
2.5 Retinoids. 6
2.6 Mycophenolate Mofetil. 6
References. 7
3 Animal Experiments and Adverse Drug Reaction Reports. 9
3.1 Animal Experiments. 9
3.2 Adverse Drug Reaction Reports. 11
References. 15
4 Some Epidemiological Principles. 17
4.1 Population Studies. 17
4.2 Case-Control Studies. 18
4.3 Cohort Studies. 20
4.4 Comparison Between Case-Control and Cohort Studies. 21
4.5 Nested Case-Control Studies. 22
4.6 The Sibling Approach. 22
References. 23
5 Pregnancy Outcomes with the Exception of Congenital
Malformations. 25
5.1 Maternal Pregnancy Complications. 25
5.1.1 Preeclampsia. 25
5.1.2 Placenta Previa. 26
5.1.3 Placenta Abruption. 26
5.1.4 Other Pregnancy Complications. 27
5.2 Spontaneous Abortion.
5.3 Stillbirth and Infant Death.
5.4 Gestational Duration and Birth Weight.
5.5 Intrauterine Growth.
5.6 Other Body Dimensions.
5.7 Perinatal Morbidity.
5.8 Long-Term Effects.
References.
Congenital Malformations.
6.1 Definition.
6.2 Major and Minor Malformations.
6.3 Single and Multiple Malformations.
6.4 Causes of Congenital Malformations.
6.4.1 Genetics.
6.4.2 Chromosome Anomalies.
6.4.3 External Factors.
6.5 Sources of Information on Malformations.
6.6 Prenatal Diagnosis and Induced Abortion.
6.7 Grouping of Congenital Malformations.
References.
Identification of Maternal Use of Drugs.
7.1 Questionnaires or Interviews in a Case-Control Setting
7.2 Prospective Randomized Studies.
7.3 Teratology Information Services TIS.
7.4 Prospective Studies of Pregnant Populations.
7.5 Pregnancy Registers.
7.6 The Swedish Medical Birth Register.
7.7 Prescription Registers.
7.8 The Effect of Errors in Drug Exposure Ascertainment.
7.9 Information on Dosage of Drugs Used.
References.
The Problem of Confounding.
8.1 Mediating Factors Should Not Be Adjusted for.
8.2 Some Common and Sometimes Important Confounders
8.2.1 Year of Birth.
8.2.2 Maternal Age.
8.2.3 Parity and Gravidity.
8.2.4 Smoking.
8.2.5 Use of Alcohol.
8.2.6 Overweight and Obesity.
8.2.7 Subfertility.
8.2.8 Race Nationality. 65
8.2.9 Socioeconomic Level. 66
8.2.10 Geography. 68
8.2.11 Previous Reproductive History. 68
8.2.12 Infant Sex. 70
8.2.13 Concomitant Maternal Disease and Drug Use. 71
8.2.14 Confounding by Indication. 71
8.3 Interaction Between Confounders. 73
8.4 Residual Confounding. 75
References. 75
9 Statistics for Dummies. 77
9.1 Risk Estimates. 77
9.2 Is the Odds Ratio or Risk Ratio Statistically Significant. 78
9.3 The Confidence Interval. 80
9.4 Expected Numbers. 80
9.5 Dealing with Confounders. 81
9.5.1 Matching. 82
9.5.2 Adjustment. 83
9.6 Survival Analysis. 84
9.7 Power Analysis. 84
9.8 The p-value and Mass Significance. 86
References. 87
10 Lumping or Splitting. 89
10.1 Lumping or Splitting of Drug Exposures. 89
10.2 Lumping or Splitting of Outcomes. 89
References. 91
11 Timing of Drug Use and Effects on the Embryo or Fetus. 93
11.1 Exposure Before Conception. 93
11.2 Period of Organogenesis First Trimester Exposure. 94
11.3 Exposure After the First Trimester. 96
References. 97
12 Repeated Studies and Meta-analyses. 99
References. 102
13 The Identification of Risks and the Information Problem. 105
13.1 Pharmacovigilance. 105
13.2 Information on the Risk with Drug Use During Pregnancy. 106
13.3 Concluding Remarks How to Evaluate a Published Study. 110
References.
2 The Alert Clinician”. 3
2.1 Thalidomide. 4
2.2 Anticonvulsants. 4
2.3 Warfarin. 5
2.4 Drugs for Thyrotoxicosis. 5
2.5 Retinoids. 6
2.6 Mycophenolate Mofetil. 6
References. 7
3 Animal Experiments and Adverse Drug Reaction Reports. 9
3.1 Animal Experiments. 9
3.2 Adverse Drug Reaction Reports. 11
References. 15
4 Some Epidemiological Principles. 17
4.1 Population Studies. 17
4.2 Case-Control Studies. 18
4.3 Cohort Studies. 20
4.4 Comparison Between Case-Control and Cohort Studies. 21
4.5 Nested Case-Control Studies. 22
4.6 The Sibling Approach. 22
References. 23
5 Pregnancy Outcomes with the Exception of Congenital
Malformations. 25
5.1 Maternal Pregnancy Complications. 25
5.1.1 Preeclampsia. 25
5.1.2 Placenta Previa. 26
5.1.3 Placenta Abruption. 26
5.1.4 Other Pregnancy Complications. 27
5.2 Spontaneous Abortion.
5.3 Stillbirth and Infant Death.
5.4 Gestational Duration and Birth Weight.
5.5 Intrauterine Growth.
5.6 Other Body Dimensions.
5.7 Perinatal Morbidity.
5.8 Long-Term Effects.
References.
Congenital Malformations.
6.1 Definition.
6.2 Major and Minor Malformations.
6.3 Single and Multiple Malformations.
6.4 Causes of Congenital Malformations.
6.4.1 Genetics.
6.4.2 Chromosome Anomalies.
6.4.3 External Factors.
6.5 Sources of Information on Malformations.
6.6 Prenatal Diagnosis and Induced Abortion.
6.7 Grouping of Congenital Malformations.
References.
Identification of Maternal Use of Drugs.
7.1 Questionnaires or Interviews in a Case-Control Setting
7.2 Prospective Randomized Studies.
7.3 Teratology Information Services TIS.
7.4 Prospective Studies of Pregnant Populations.
7.5 Pregnancy Registers.
7.6 The Swedish Medical Birth Register.
7.7 Prescription Registers.
7.8 The Effect of Errors in Drug Exposure Ascertainment.
7.9 Information on Dosage of Drugs Used.
References.
The Problem of Confounding.
8.1 Mediating Factors Should Not Be Adjusted for.
8.2 Some Common and Sometimes Important Confounders
8.2.1 Year of Birth.
8.2.2 Maternal Age.
8.2.3 Parity and Gravidity.
8.2.4 Smoking.
8.2.5 Use of Alcohol.
8.2.6 Overweight and Obesity.
8.2.7 Subfertility.
8.2.8 Race Nationality. 65
8.2.9 Socioeconomic Level. 66
8.2.10 Geography. 68
8.2.11 Previous Reproductive History. 68
8.2.12 Infant Sex. 70
8.2.13 Concomitant Maternal Disease and Drug Use. 71
8.2.14 Confounding by Indication. 71
8.3 Interaction Between Confounders. 73
8.4 Residual Confounding. 75
References. 75
9 Statistics for Dummies. 77
9.1 Risk Estimates. 77
9.2 Is the Odds Ratio or Risk Ratio Statistically Significant. 78
9.3 The Confidence Interval. 80
9.4 Expected Numbers. 80
9.5 Dealing with Confounders. 81
9.5.1 Matching. 82
9.5.2 Adjustment. 83
9.6 Survival Analysis. 84
9.7 Power Analysis. 84
9.8 The p-value and Mass Significance. 86
References. 87
10 Lumping or Splitting. 89
10.1 Lumping or Splitting of Drug Exposures. 89
10.2 Lumping or Splitting of Outcomes. 89
References. 91
11 Timing of Drug Use and Effects on the Embryo or Fetus. 93
11.1 Exposure Before Conception. 93
11.2 Period of Organogenesis First Trimester Exposure. 94
11.3 Exposure After the First Trimester. 96
References. 97
12 Repeated Studies and Meta-analyses. 99
References. 102
13 The Identification of Risks and the Information Problem. 105
13.1 Pharmacovigilance. 105
13.2 Information on the Risk with Drug Use During Pregnancy. 106
13.3 Concluding Remarks How to Evaluate a Published Study. 110
References.