Organization of Teratology Information Services (OTIS) Autoimmune Diseases in Pregnancy Project

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of etanercept when used in the first trimester of pregnancy with respect to major structural birth defects of newborns. This is an observational study only - no investigational product is used.

Detailed Description
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This pregnancy registry cohort study will be conducted by the Organization of Teratology Information Specialists (OTIS) which is a network of university and health department based telephone information centers serving pregnant women and health care providers throughout North America. Participants in the first two cohorts are recruited concurrently from callers to OTIS centers, from health care providers and through direct to consumer marketing efforts. The source of historical controls is archived data on pregnancies that have been followed through the California Teratogen Information Service's Clinical Research Program located at the University of California San Diego.

Official Title
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OTIS Autoimmune Diseases in Pregnancy Project

Conditions
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Pregnancy

Intervention / Treatment
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* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Cohort 1 Inclusion Criteria: Eligible subjects will be currently pregnant women residing in the US or Canada who have had any exposure to etanercept for treatment of Rheumatoid Arthritis (RA), Juvenile RA, Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsoA) or Psoriasis (PsO) at any time during the first trimester of pregnancy which is defined as the period between first day of the last menstrual period (i.e., within two weeks of conception) up to and including the 12th week after the first day of the last menstrual period (LMP) - Eligible subjects must have documentation of an exposure to etanercept during the first trimester of pregnancy. Cohort 2 Inclusion Criteria: Eligible subjects will be currently pregnant women residing in the US or Canada who have not taken etanercept or any TNF antagonist for treatment of RA, JRA, AS, PsoA or PsO at any time in the current pregnancy or within two months prior to the first day of the last menstrual period (LMP). Cohort 3 Inclusion Criteria: Eligible subjects will be pregnant women who were residing in the US or Canada who had not been diagnosed with RA, JRA, AS, PsoA or PsO and had not been exposed to a known human teratogen during the index pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Etanercept-Exposed<br>Pregnant women with a current diagnosis of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), psoriatic arthritis (PsoA) or psoriasis (PsO) who used etanercept in the first trimester of pregnancy for any length of time. | Drug: Etanercept<br>* Pregnant women previously exposed to etanercept during the first trimester. Etanercept was not administered in this non-interventional study.<br>* Other names: Enbrel;|
| Diseased Controls<br>Pregnant women with a current diagnosis of RA, JRA, AS, PsA, or PsO who did not use etanercept or any tumor necrosis factor (TNF) antagonist during pregnancy. | |
| Non-Diseased Historical Comparison<br>Pregnant women not diagnosed with RA, JRA, AS, PsoA, or PsO who did not use etanercept or any TNF antagonist at any time in pregnancy and were not exposed to any known human teratogen during pregnancy. This cohort consists of historical controls enrolled in other pregnancy outcome studies selected to match pregnant women in the exposed cohort. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Infants With Major Birth Defects in Pregnancies Ending With Live-born Infants | A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (e.g., a cleft lip). The Registry used the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system, with some specified modifications that are appropriate for cohort studies as opposed to case-control studies. | From birth through 1 year of age | 
| Percentage of Infants With Major Birth Defects in All Pregnancies | A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (e.g., a cleft lip). The Registry used the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system, with some specified modifications that are appropriate for cohort studies as opposed to case-control studies. | From birth through 1 year of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Infants With Any 3 or More Minor Birth Defects | A minor structural defect is defined as a defect which occurs in less than 4 percent of the population but which has neither cosmetic nor functional significance to the child (e.g., complete 2,3 syndactyly of the toes). The Registry used the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system, with some specified modifications that are appropriate for cohort studies as opposed to case-control studies. | From birth through 1 year of age | 
| Percentage of Infants With a Specific Pattern of Any 3 or More Minor Birth Defects | A minor structural defect is defined as a defect which occurs in less than 4 percent of the population but which has neither cosmetic nor functional significance to the child (e.g., complete 2,3 syndactyly of the toes). A pattern is defined as at least the same 3 specific minor malformations occurring in at least two infants in the exposed group. | From birth through 1 year of age | 
| Percentage of Pregnancies Ending in Spontaneous Abortion | Computed using Kaplan-Meier estimate at 20 weeks gestation, accounting for left truncation due to varying time in gestation at enrollment. In multiple pregnancies ending in at least 1 live-born infant, the live birth outcome is included in the analysis. In multiples ending in no live birth outcomes, the spontaneous abortion is counted as 1 event. | 9 months | 
| Percentage of Participants With Pre-term Delivery | A pretem delivery is defined as prior to 37 weeks gestation. Computed using Kaplan-Meier estimate at 37 weeks' gestation, accounting for left truncation due to varying time in gestation at enrollment. Multiple births are excluded. | 9 months | 
| Gestational Age at Delivery (GAD) of Live Births |  | At birth | 
| Birth Weight Among Full Term Infants |  | At birth | 
| Birth Length Among Full Term Infants |  | At birth | 
| Birth Head Circumference Among Full Term Infants |  | At birth | 
| Percentage of Infants With Small for Gestational Age Birth Weight | Small for gestational age is defined as ≤ 10th percentile for sex and gestational age using National Center for Health Statistics (NCHS) / Center for Disease Control (CDC) growth curves. | At birth | 
| Percentage of Infants With Small for Gestational Age Birth Length | Small for gestational age is defined as ≤ 10th percentile for sex and gestational age using National Center for Health Statistics (NCHS) / Center for Disease Control (CDC) growth curves. | At birth | 
| Percentage of Infants With Small for Gestational Age Birth Head Circumference | Small for gestational age is defined as ≤ 10th percentile for sex and gestational age using National Center for Health Statistics (NCHS) / Center for Disease Control (CDC) growth curves. | At birth | 
| Postnatal Weight Percentile at One Year |  | 1 year after birth | 
| Postnatal Length Percentile at One Year |  | 1 year after birth | 
| Postnatal Head Circumference Percentile at One Year |  | 1 year after birth | 
| Percentage of Infants at One Year of Age With Small for Gestational Age Weight | Postnatal growth deficiency defined as ≤ 10th centile for chronological age. Age adjusted for gestational age at delivery if child was less than 12 months of age at postnatal measurement, unadjusted if ≥ 12 months of age at postnatal measurement. | 1 year after birth | 
| Percentage of Infants at One Year of Age With Small for Gestational Age Length | Postnatal growth deficiency defined as ≤ 10th centile for chronological age. Age adjusted for gestational age at delivery if child was less than 12 months of age at postnatal measurement, unadjusted if ≥ 12 months of age at postnatal measurement. | 1 year after birth | 
| Percentage of Infants at One Year of Age With Small for Gestational Age Head Circumference | Postnatal growth deficiency defined as ≤ 10th centile for chronological age. Age adjusted for gestational age at delivery if child was less than 12 months of age at postnatal measurement, unadjusted if ≥ 12 months of age at postnatal measurement. | 1 year after birth | 
| Percentage of Infants With Reported Serious or Opportunistic Infections Through One Year |  | From birth to 1 year | 
| Percentage of Infants Diagnosed With Any Malignancy Through One Year of Age |  | From birth to 1 year | 
| Percentage of Infants With Abnormal Results on Ages and Stages Questionnaire (ASQ) | The ASQ-3 evaluates 5 domains of development: communication, gross motor, fine motor, problem solving, and personal-social. Each domain has a set of 6 items and parents rate the most appropriate answer for the presence of each skill: Yes, Sometimes, Not Yet, with point values of 10, 5, or 0, respectively. Each domain question set is totaled independently and compared against statistically derived cutoffs that are set at 2 standard deviations below the mean. The percentage of infants below the cut-off or close to the cutoff (borderline) is reported. | 1 year after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, Autoimmune Disease