Birth Defect, Low Birth Weight, Spontaneous Abortions
Conditions
Brief summary
US study to estimate the prevalence at birth of major birth defects (ie, those that cause significant functional or cosmetic impairment, require surgery, or are life-limiting) in children born to mothers who have received Nplate® therapy at any time during the pregnancy.
Detailed description
The purpose of the NPER is to monitor pregnancies exposed to Nplate® and to detect and record serious adverse events in infants up to one year after birth. The lack of adequate human fetal safety data for Nplate® makes the NPER an important component of the pharmacovigilance program on the safety of this drug. With respect to fetal outcome, it is important to evaluate the spectrum of outcomes that may be relevant to a medication exposure during pregnancy, and these include both easily recognizable defects that are visible at birth, as well as more subtle or delayed defects that may not be readily identifiable without special expertise and observation beyond the newborn period.
Interventions
DRUGNot applicable- observational study
Sponsors
Amgen
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Healthy volunteers
No
Inclusion criteria
* Eligible subjects will be currently pregnant women residing in the US who: Have had any exposure to Nplate® at any time during the pregnancy, which is defined as the period between first day of the last menstrual period (LMP) (ie, within two weeks of conception) up to any date before the date of delivery or end of the pregnancy. The date of conception will be defined as fourteen days prior to the next expected menstrual period for women who report a regular menstrual cycle. If the date of the first day of the LMP is unclear, or if the estimated date of conception as determined by a first-trimester ultrasound differs by more than one week from the date as determined by the first day of LMP, the first-trimester ultrasound-derived date will be used to estimate the timing of exposure to Nplate®, as well as timing of enrollment. If neither a clear date of the first day of the LMP nor a first-trimester ultrasound is available, the estimated date of conception for purposes of enrollment will be determined by best estimate of the woman's prenatal care provider. * Agree to enroll at any time from the estimated date of conception up to any date before the date of delivery or end of the pregnancy and who have not already had prenatal diagnosis of any major structural birth defect in the current pregnancy prior to enrollment. * Agree to provide consent for participation in the registry including follow-up interviews.
Exclusion criteria
* Subjects will be ineligible for study participation if any of the following apply: * Exposure to Nplate® did not occur during pregnancy. * Prior knowledge of prenatal diagnosis of a birth defect. Patients who fall under this category will be encouraged to call the Amgen PSP toll free number for enrollment and follow-up. * Cases reported to the NPER after completion of the exposed pregnancy. Patients who fall under this category will be encouraged to call the Amgen PSP toll free number for enrollment and follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Children Born With Major Birth Defects | At birth | An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (eg, a cleft lip), require surgery, or are life-limiting). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Spontaneous and Elective Abortions or Stillbirths | 9 months (during pregnancy) | Number of each of spontaneous abortions, elective abortions, and stillbirths among mothers who received Nplate® therapy at any time during the pregnancy. |
| Number of Children With Preterm Birth or Low Birth Weight | At birth | Number of children with preterm birth (\<37 weeks gestation) or low birth weight (\<2,500 grams) among children born to mothers who have received Nplate® therapy at any time during the pregnancy. |
| Number of Children Born With Any 3 or More Minor Birth Defects | At birth | An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A minor structural defect is defined as a defect which occurs in less than 4% of the population but which has neither cosmetic nor functional significance to the child (eg, complete 2,3 syndactyly of the toes). |
| Number of Children Born With Intrauterine Growth Restriction | At birth | Number of children born with intrauterine growth restriction (weight, length or head circumference less than tenth percentile for sex and gestational age) among mothers who have received Nplate® therapy at any time during the pregnancy. |
| Number of Infants With Adverse Events | 12 months from birth | In the first year of life, the incidence of all serious adverse events, as well as of nevi (birthmarks) and angiomata (benign tumors with blood vessels or lymph vessels), among infants whose mothers received Nplate® therapy at any time during the pregnancy. |
| Number of Participants With Adverse Events | Throughout pregnancy and for up to 6 weeks after delivery | — |
| Number of Children Born With a Specific Pattern of Minor Birth Defects | At birth | Only those infants who have received medical evaluation and who have three or more minor defects will be considered affected for purposes of the evaluation of a pattern of minor defects. |
Participant flow
Recruitment details
The registry was initiated in May 2009. The first participant enrolled in June 2010 and the last participant enrolled in December 2013. Eligible participants were currently pregnant women residing in the United States who had any exposure to Nplate at any time during pregnancy.
Pre-assignment details
The Nplate® Pregnancy Exposure Registry (NPER) was to continue the follow-up of enrollees until April 2016; however, the NPER was terminated on 24 January 2014 because of the low number of participants enrolled.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Pregnant woman who had any exposure to Nplate® at any time during pregnancy. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 4 / 4 | 2 / 4 |
Outcome results
Primary
Number of Children Born With Major Birth Defects
An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (eg, a cleft lip), require surgery, or are life-limiting).
Time frame: At birth
Population: Children born to enrolled participants during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Children Born With Major Birth Defects | 0 children |
Secondary
Number of Children Born With Any 3 or More Minor Birth Defects
An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A minor structural defect is defined as a defect which occurs in less than 4% of the population but which has neither cosmetic nor functional significance to the child (eg, complete 2,3 syndactyly of the toes).
Time frame: At birth
Population: Children born to enrolled participants during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Children Born With Any 3 or More Minor Birth Defects | 0 children |
Secondary
Number of Children Born With a Specific Pattern of Minor Birth Defects
Only those infants who have received medical evaluation and who have three or more minor defects will be considered affected for purposes of the evaluation of a pattern of minor defects.
Time frame: At birth
Population: Children born with 3 or more minor birth defects
Secondary
Number of Children Born With Intrauterine Growth Restriction
Number of children born with intrauterine growth restriction (weight, length or head circumference less than tenth percentile for sex and gestational age) among mothers who have received Nplate® therapy at any time during the pregnancy.
Time frame: At birth
Population: Children born to enrolled participants during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Children Born With Intrauterine Growth Restriction | 1 children |
Secondary
Number of Children With Preterm Birth or Low Birth Weight
Number of children with preterm birth (\<37 weeks gestation) or low birth weight (\<2,500 grams) among children born to mothers who have received Nplate® therapy at any time during the pregnancy.
Time frame: At birth
Population: Children born to enrolled participants during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Number of Children With Preterm Birth or Low Birth Weight | Preterm birth | 1 children |
| All Participants | Number of Children With Preterm Birth or Low Birth Weight | Low birth weight | 1 children |
Secondary
Number of Infants With Adverse Events
In the first year of life, the incidence of all serious adverse events, as well as of nevi (birthmarks) and angiomata (benign tumors with blood vessels or lymph vessels), among infants whose mothers received Nplate® therapy at any time during the pregnancy.
Time frame: 12 months from birth
Population: Children born to enrolled participants during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Number of Infants With Adverse Events | Serious adverse events | 2 infants |
| All Participants | Number of Infants With Adverse Events | Nevi | 0 infants |
| All Participants | Number of Infants With Adverse Events | Angiomata | 0 infants |
Secondary
Number of Participants With Adverse Events
Time frame: Throughout pregnancy and for up to 6 weeks after delivery
Population: All enrolled participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Participants With Adverse Events | 4 participants |
Secondary
Number of Participants With Spontaneous and Elective Abortions or Stillbirths
Number of each of spontaneous abortions, elective abortions, and stillbirths among mothers who received Nplate® therapy at any time during the pregnancy.
Time frame: 9 months (during pregnancy)
Population: All enrolled participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Number of Participants With Spontaneous and Elective Abortions or Stillbirths | Spontaneous abortions | 0 participants |
| All Participants | Number of Participants With Spontaneous and Elective Abortions or Stillbirths | Elective abortions | 0 participants |
| All Participants | Number of Participants With Spontaneous and Elective Abortions or Stillbirths | Stillbirths | 0 participants |