Pregnancy
Conditions
Keywords
pregnancy, Autoimmune Disease
Brief summary
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
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.
Interventions
DRUGEtanercept
Pregnant women previously exposed to etanercept during the first trimester. Etanercept was not administered in this non-interventional study.
Sponsors
Amgen
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Infants With Major Birth Defects in Pregnancies Ending With Live-born Infants | From birth through 1 year of age | 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. |
| Percentage of Infants With Major Birth Defects in All Pregnancies | From birth through 1 year of age | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Infants With a Specific Pattern of Any 3 or More Minor Birth Defects | From birth through 1 year of age | 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. |
| Percentage of Participants With Pre-term Delivery | 9 months | 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. |
| 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 | At birth | 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. |
| Percentage of Infants With Small for Gestational Age Birth Length | At birth | 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. |
| Percentage of Infants With Small for Gestational Age Birth Head Circumference | At birth | 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. |
| Percentage of Pregnancies Ending in Spontaneous Abortion | 9 months | 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. |
| 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 | 1 year after birth | 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. |
| Percentage of Infants at One Year of Age With Small for Gestational Age Length | 1 year after birth | 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. |
| Percentage of Infants at One Year of Age With Small for Gestational Age Head Circumference | 1 year after birth | 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. |
| 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) | 1 year after birth | 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. |
| Postnatal Weight Percentile at One Year | 1 year after birth | — |
| Percentage of Infants With Any 3 or More Minor Birth Defects | From birth through 1 year of age | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited concurrently from callers to Organization of Teratology Information Specialists (OTIS) centers, from health care providers and through direct to consumer marketing efforts. A third cohort of historical controls including 296 women was also included in the study but are not included in the results of this report.
Pre-assignment details
The first participant was recruited in April, 2005 and recruitment continued through March 19, 2012.
Participants by arm
| Arm | Count |
|---|---|
| Etanercept-Exposed 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. | 370 |
| Diseased Controls 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. | 164 |
| Total | 534 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 6 |
Baseline characteristics
| Characteristic | Etanercept-Exposed | Diseased Controls | Total |
|---|---|---|---|
| Age, Customized 25 - 29 years | 81 participants | 34 participants | 115 participants |
| Age, Customized < 25 years | 21 participants | 7 participants | 28 participants |
| Age, Customized 30 - 34 years | 132 participants | 48 participants | 180 participants |
| Age, Customized > 34 years | 136 participants | 75 participants | 211 participants |
| Alcohol Use During Pregnancy No | 193 participants | 84 participants | 277 participants |
| Alcohol Use During Pregnancy Yes | 177 participants | 80 participants | 257 participants |
| Any Previous Child with Birth Defect No | 350 participants | 156 participants | 506 participants |
| Any Previous Child with Birth Defect Yes | 20 participants | 8 participants | 28 participants |
| Disease Severity Score - PsO | 2.0 units on a scale STANDARD_DEVIATION 1.5 | 1.9 units on a scale STANDARD_DEVIATION 1.1 | 1.9 units on a scale STANDARD_DEVIATION 1.4 |
| Disease Severity Score - RA | 0.5 units on a scale STANDARD_DEVIATION 0.6 | 0.6 units on a scale STANDARD_DEVIATION 0.6 | 0.5 units on a scale STANDARD_DEVIATION 0.6 |
| Duration of Disease | 9.8 years STANDARD_DEVIATION 7.9 | 10.0 years STANDARD_DEVIATION 9.1 | 9.9 years STANDARD_DEVIATION 8.3 |
| Exposed to Etanercept 2nd and/or 3rd Trimester Only | 13 participants | 0 participants | 13 participants |
| Exposed to Etanercept First Trimester | 344 participants | 0 participants | 344 participants |
| Exposed to Etanercept Last Menstrual Period to Date of Conception | 8 participants | 0 participants | 8 participants |
| Exposed to Etanercept Started Prior to DOC, End Date Unavailable | 5 participants | 0 participants | 5 participants |
| Geographic Area of Residence Canada | 31 participants | 27 participants | 58 participants |
| Geographic Area of Residence Missing | 1 participants | 1 participants | 2 participants |
| Geographic Area of Residence United States | 338 participants | 136 participants | 474 participants |
| Gestational Age at Time of Enrollment 13 - 19.9 weeks | 99 participants | 58 participants | 157 participants |
| Gestational Age at Time of Enrollment < 13 weeks | 196 participants | 84 participants | 280 participants |
| Gestational Age at Time of Enrollment ≥ 20 weeks | 75 participants | 22 participants | 97 participants |
| Gravidity Category 1 pregnancy | 135 participants | 62 participants | 197 participants |
| Gravidity Category 2 -3 pregnancies | 163 participants | 78 participants | 241 participants |
| Gravidity Category 4 -5 pregnancies | 60 participants | 21 participants | 81 participants |
| Gravidity Category ≥ 6 pregnancies | 12 participants | 3 participants | 15 participants |
| Hollingshead Socioeconomic Category 1 | 134 participants | 69 participants | 203 participants |
| Hollingshead Socioeconomic Category 2 | 145 participants | 67 participants | 212 participants |
| Hollingshead Socioeconomic Category 3 | 59 participants | 19 participants | 78 participants |
| Hollingshead Socioeconomic Category 4 | 23 participants | 6 participants | 29 participants |
| Hollingshead Socioeconomic Category 5 | 7 participants | 3 participants | 10 participants |
| Hollingshead Socioeconomic Category Missing | 2 participants | 0 participants | 2 participants |
| Intended Pregnancy No | 106 participants | 41 participants | 147 participants |
| Intended Pregnancy Yes | 264 participants | 123 participants | 387 participants |
| In Vitro Fertilization (IVF) with This Pregnancy No | 343 participants | 159 participants | 502 participants |
| In Vitro Fertilization (IVF) with This Pregnancy Yes | 27 participants | 5 participants | 32 participants |
| Major Known or Suspected Human Teratogens No | 356 participants | 153 participants | 509 participants |
| Major Known or Suspected Human Teratogens Yes | 14 participants | 11 participants | 25 participants |
| Maternal Comorbidities Antidepressant Medication Use in Any Trimester | 28 participants | 14 participants | 42 participants |
| Maternal Comorbidities Asthma | 48 participants | 33 participants | 81 participants |
| Maternal Comorbidities Infections | 274 participants | 114 participants | 388 participants |
| Maternal Comorbidities Other Autoimmune Disease | 43 participants | 17 participants | 60 participants |
| Maternal Comorbidities Other Psychiatric Conditions | 64 participants | 32 participants | 96 participants |
| Maternal Comorbidities Preeclampsia | 11 participants | 8 participants | 19 participants |
| Maternal Comorbidities Pre-gestational Hypertension | 19 participants | 10 participants | 29 participants |
| Maternal Comorbidities Thyroid Disease | 45 participants | 23 participants | 68 participants |
| Maternal Education 12 - 15 years | 118 participants | 42 participants | 160 participants |
| Maternal Education < 12 years | 9 participants | 4 participants | 13 participants |
| Maternal Education > 15 years | 243 participants | 118 participants | 361 participants |
| Parity Category 0 births | 193 participants | 88 participants | 281 participants |
| Parity Category 1 -2 births | 153 participants | 69 participants | 222 participants |
| Parity Category 3 - 4 births | 22 participants | 7 participants | 29 participants |
| Parity Category ≥ 5 births | 2 participants | 0 participants | 2 participants |
| Prednisone and/or Systemic Oral Corticosteroid No | 207 participants | 99 participants | 306 participants |
| Prednisone and/or Systemic Oral Corticosteroid Yes | 163 participants | 65 participants | 228 participants |
| Prenatal Multivitamin or Folic Acid Supplements Began Prior to Conception | 217 participants | 114 participants | 331 participants |
| Prenatal Multivitamin or Folic Acid Supplements Not Taken at All | 5 participants | 0 participants | 5 participants |
| Prenatal Multivitamin or Folic Acid Supplements Post-conception Only | 148 participants | 50 participants | 198 participants |
| Pre-pregnancy Body Weight | 70.2 kg STANDARD_DEVIATION 18.14 | 68.3 kg STANDARD_DEVIATION 16.5 | 69.6 kg STANDARD_DEVIATION 17.8 |
| Pre-pregnancy Height | 164.7 cm STANDARD_DEVIATION 7.1 | 166.7 cm STANDARD_DEVIATION 7 | 165.3 cm STANDARD_DEVIATION 7.1 |
| Previous Elective Terminations 0 | 314 participants | 150 participants | 464 participants |
| Previous Elective Terminations 1 | 49 participants | 12 participants | 61 participants |
| Previous Elective Terminations 2 | 5 participants | 1 participants | 6 participants |
| Previous Elective Terminations ≥ 3 | 2 participants | 1 participants | 3 participants |
| Previous Preterm Delivery No | 333 participants | 158 participants | 491 participants |
| Previous Preterm Delivery Yes | 37 participants | 6 participants | 43 participants |
| Previous Spontaneous Abortion 0 | 265 participants | 117 participants | 382 participants |
| Previous Spontaneous Abortion 1 | 73 participants | 30 participants | 103 participants |
| Previous Spontaneous Abortion 2 | 22 participants | 11 participants | 33 participants |
| Previous Spontaneous Abortion ≥ 3 | 10 participants | 6 participants | 16 participants |
| Primary Disease (RA, JRA, PsA or AS) No | 59 participants | 47 participants | 106 participants |
| Primary Disease (RA, JRA, PsA or AS) Yes | 311 participants | 117 participants | 428 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 18 participants | 6 participants | 24 participants |
| Race/Ethnicity, Customized Black | 14 participants | 3 participants | 17 participants |
| Race/Ethnicity, Customized Hispanic | 42 participants | 13 participants | 55 participants |
| Race/Ethnicity, Customized Native American | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Non-Hispanic White | 292 participants | 138 participants | 430 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Referral Source Category Health-care Professional (HCP) | 185 participants | 53 participants | 238 participants |
| Referral Source Category Internet | 65 participants | 27 participants | 92 participants |
| Referral Source Category Missing | 1 participants | 0 participants | 1 participants |
| Referral Source Category Other | 53 participants | 10 participants | 63 participants |
| Referral Source Category OTIS Member Service | 29 participants | 69 participants | 98 participants |
| Referral Source Category Patient Support Group | 0 participants | 4 participants | 4 participants |
| Referral Source Category Sponsor | 37 participants | 1 participants | 38 participants |
| Sex: Female, Male Female | 370 Participants | 164 Participants | 534 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Tobacco Use During Pregnancy No | 330 participants | 147 participants | 477 participants |
| Tobacco Use During Pregnancy Yes | 40 participants | 17 participants | 57 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 18 / 164 | 37 / 370 | 12 / 146 | 59 / 352 |
Outcome results
Primary
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.
Time frame: From birth through 1 year of age
Population: Includes multiple pregnancies counted as 1 outcome; any 1 or more malformed infant counted as 1 major malformation in the numerator and 1 outcome in the denominator. Excludes 9 lost-to-follow-up in Etanercept-Exposed and 6 in Diseased Controls cohort. Only women exposed to etanercept in 1st trimester are included in the Etanercept-Exposed cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Major Birth Defects in All Pregnancies | 9.9 percentage of participants |
| Diseased Controls | Percentage of Infants With Major Birth Defects in All Pregnancies | 4.4 percentage of participants |
95% CI: [1.02, 5.52]
Primary
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.
Time frame: From birth through 1 year of age
Population: Includes multiple pregnancies ending in at least 1 live-born infant; any 1 or more malformed live-born infants counted as 1 major malformation outcome in the numerator, and 1 pregnancy outcome in the denominator. Only women exposed to etanercept in the 1st trimester are included in the Etanercept-Exposed cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Major Birth Defects in Pregnancies Ending With Live-born Infants | 9.4 percentage of participants |
| Diseased Controls | Percentage of Infants With Major Birth Defects in Pregnancies Ending With Live-born Infants | 3.5 percentage of participants |
95% CI: [1.04, 7.35]
Secondary
Birth Head Circumference Among Full Term Infants
Time frame: At birth
Population: Live birth full-term infants, excluding multiple births, where data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Birth Head Circumference Among Full Term Infants | 34.4 cm | Standard Deviation 1.6 |
| Diseased Controls | Birth Head Circumference Among Full Term Infants | 34.5 cm | Standard Deviation 1.5 |
95% CI: [-0.43, 0.26]
Secondary
Birth Length Among Full Term Infants
Time frame: At birth
Population: Live birth full-term infants, excluding multiple births, where data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Birth Length Among Full Term Infants | 50.8 cm | Standard Deviation 2.6 |
| Diseased Controls | Birth Length Among Full Term Infants | 50.7 cm | Standard Deviation 2.4 |
95% CI: [-0.44, 0.63]
Secondary
Birth Weight Among Full Term Infants
Time frame: At birth
Population: Live birth full-term infants, excluding multiple births, where data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Birth Weight Among Full Term Infants | 3399.1 g | Standard Deviation 434.9 |
| Diseased Controls | Birth Weight Among Full Term Infants | 3380.2 g | Standard Deviation 447 |
95% CI: [-83.32, 126.91]
Secondary
Gestational Age at Delivery (GAD) of Live Births
Time frame: At birth
Population: Live births in women enrolled and exposed to etanercept prior to 37 weeks' gestation (Etanercept-Exposed) or enrolled prior to 37 weeks gestation (Diseased Controls), excluding multiple births.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Gestational Age at Delivery (GAD) of Live Births | 38.6 weeks | Standard Deviation 2.2 |
| Diseased Controls | Gestational Age at Delivery (GAD) of Live Births | 38.8 weeks | Standard Deviation 2 |
95% CI: [-0.65, 0.26]
Secondary
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.
Time frame: 1 year after birth
Population: Live-born infants, excluding multiple births, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants at One Year of Age With Small for Gestational Age Head Circumference | 4.1 percentage of infants |
| Diseased Controls | Percentage of Infants at One Year of Age With Small for Gestational Age Head Circumference | 4.6 percentage of infants |
95% CI: [0.29, 2.65]
Secondary
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.
Time frame: 1 year after birth
Population: Live-born infants, excluding multiple births, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants at One Year of Age With Small for Gestational Age Length | 7.2 percentage of infants |
| Diseased Controls | Percentage of Infants at One Year of Age With Small for Gestational Age Length | 5.5 percentage of infants |
95% CI: [0.43, 3.14]
Secondary
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.
Time frame: 1 year after birth
Population: Live-born infants, excluding multiple births, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants at One Year of Age With Small for Gestational Age Weight | 14.5 percentage of infants |
| Diseased Controls | Percentage of Infants at One Year of Age With Small for Gestational Age Weight | 13.9 percentage of infants |
95% CI: [0.37, 1.62]
Secondary
Percentage of Infants Diagnosed With Any Malignancy Through One Year of Age
Time frame: From birth to 1 year
Population: Live-born infants, including singletons and 1 randomly selected twin from multiple pregnancies, born to enrolled women exposed to etanercept at any time during pregnancy (Etanercept-Exposed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants Diagnosed With Any Malignancy Through One Year of Age | 0 Percentage of infants |
| Diseased Controls | Percentage of Infants Diagnosed With Any Malignancy Through One Year of Age | 0 Percentage of infants |
Secondary
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.
Time frame: 1 year after birth
Population: Live-born infants, including singletons and 1 randomly selected twin from multiple pregnancies, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Abnormal Results on Ages and Stages Questionnaire (ASQ) | 28.2 Percentage of infants |
| Diseased Controls | Percentage of Infants With Abnormal Results on Ages and Stages Questionnaire (ASQ) | 27.4 Percentage of infants |
95% CI: [0.65, 1.69]
Secondary
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.
Time frame: From birth through 1 year of age
Population: Children born to enrolled participants during the study who received the dysmorphological exam. Includes singletons and 1 randomly selected twin from twin pairs. Only women exposed to etanercept in the 1st trimester are included in the Etanercept-Exposed cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Any 3 or More Minor Birth Defects | 25.7 percentage of infants |
| Diseased Controls | Percentage of Infants With Any 3 or More Minor Birth Defects | 22.5 percentage of infants |
95% CI: [0.7, 2.01]
Secondary
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.
Time frame: From birth through 1 year of age
Population: Children born to enrolled participants who received the dysmorphological exam. Includes multiples who received the exam for consideration of pattern; co-twins with the same 3 or more minor defects could not constitute a pattern on their own. Only women exposed to etanercept in the 1st trimester are included in the Etanercept-Exposed cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With a Specific Pattern of Any 3 or More Minor Birth Defects | 2.3 percentage of infants |
| Diseased Controls | Percentage of Infants With a Specific Pattern of Any 3 or More Minor Birth Defects | 0.0 percentage of infants |
Secondary
Percentage of Infants With Reported Serious or Opportunistic Infections Through One Year
Time frame: From birth to 1 year
Population: Live-born infants, including singletons and 1 randomly selected twin from multiple pregnancies, born to enrolled women exposed to etanercept at any time during pregnancy (Etanercept-Exposed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Reported Serious or Opportunistic Infections Through One Year | 5.3 Percentage of infants |
| Diseased Controls | Percentage of Infants With Reported Serious or Opportunistic Infections Through One Year | 4.2 Percentage of infants |
95% CI: [0.47, 4.02]
Secondary
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.
Time frame: At birth
Population: Live-born infants, excluding multiple births, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Small for Gestational Age Birth Head Circumference | 17.1 percentage of infants |
| Diseased Controls | Percentage of Infants With Small for Gestational Age Birth Head Circumference | 14.4 percentage of infants |
95% CI: [0.4, 1.57]
Secondary
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.
Time frame: At birth
Population: Live-born infants, excluding multiple births, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Small for Gestational Age Birth Length | 4.7 percentage of infants |
| Diseased Controls | Percentage of Infants With Small for Gestational Age Birth Length | 6.5 percentage of infants |
95% CI: [0.31, 1.68]
Secondary
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.
Time frame: At birth
Population: Live-born infants, excluding multiple births, where data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Infants With Small for Gestational Age Birth Weight | 6.8 percentage of infants |
| Diseased Controls | Percentage of Infants With Small for Gestational Age Birth Weight | 10.6 percentage of infants |
95% CI: [0.22, 1.05]
Secondary
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.
Time frame: 9 months
Population: Participants enrolled and exposed to etanercept prior to 37 weeks gestation (Etanercept-Exposed) or enrolled prior to 37 weeks gestation (Diseased Controls), and excluding multiple births.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Participants With Pre-term Delivery | 13.9 percentage of participants |
| Diseased Controls | Percentage of Participants With Pre-term Delivery | 10.0 percentage of participants |
95% CI: [0.86, 2.98]
Secondary
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.
Time frame: 9 months
Population: Participants enrolled and exposed to etanercept prior to 20 weeks gestation (Etanercept-Exposed) or enrolled prior to 20 weeks gestation (Diseased Controls).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept-Exposed | Percentage of Pregnancies Ending in Spontaneous Abortion | 14.7 percentage of pregnancies |
| Diseased Controls | Percentage of Pregnancies Ending in Spontaneous Abortion | 28.8 percentage of pregnancies |
95% CI: [0.2, 1.12]
Secondary
Postnatal Head Circumference Percentile at One Year
Time frame: 1 year after birth
Population: Live-born infants, excluding multiple births, where 1-year data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Postnatal Head Circumference Percentile at One Year | 63.9 percentile | Standard Deviation 28.3 |
| Diseased Controls | Postnatal Head Circumference Percentile at One Year | 63.8 percentile | Standard Deviation 27 |
95% CI: [-6.12, 6.65]
Secondary
Postnatal Length Percentile at One Year
Time frame: 1 year after birth
Population: Live-born infants, excluding multiple births, where 1-year data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Postnatal Length Percentile at One Year | 60.1 percentile | Standard Deviation 29.7 |
| Diseased Controls | Postnatal Length Percentile at One Year | 62.3 percentile | Standard Deviation 27.9 |
95% CI: [-5.76, 8.81]
Secondary
Postnatal Weight Percentile at One Year
Time frame: 1 year after birth
Population: Live-born infants, excluding multiple births, where 1-year data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept-Exposed | Postnatal Weight Percentile at One Year | 45.1 percentile | Standard Deviation 30.1 |
| Diseased Controls | Postnatal Weight Percentile at One Year | 44.1 percentile | Standard Deviation 28.6 |
95% CI: [-7.59, 7.99]