This study will utilize a prospective, observational, exposure cohort design to examine pregnancy and infant outcomes in women and infants who are exposed to siponimod during pregnancy to treat MS.
The prevalence of each outcome in women exposed to siponimod and their infants will be compared to those observed in two unexposed comparator groups: a disease-matched comparison group of women who have not used siponimod during pregnancy but have been diagnosed with MS (disease-matched unexposed comparison group), and a comparison group of healthy women who do not have diagnosis of MS, have not had exposure to a known human teratogen, and have not taken siponimod in pregnancy (healthy comparison group). Pregnant women exposed to siponimod who do not meet the prospective cohort criteria will also be followed as part of an exposure series. All participants will be recruited via voluntary participant registration following informed consent by the pregnant woman for her participation. Participants may withdraw from the study at any time.
Study Type
OBSERVATIONAL
Enrollment
867
Prospective observational cohort study. There is no treatment allocation. Patients administered siponimod, that have started before inclusion of the patient into the study will be enrolled.
Novartis Investigative Site
La Jolla, California, United States
RECRUITINGPrevalence of major structural defects
A major structural defect is defined as a defect that has either cosmetic or functional significance to the child (e.g., a cleft lip).
Time frame: Up to 10,5 years
Number of spontaneous abortion/miscarriage
Spontaneous abortion/miscarriage is defined as non-deliberate fetal death which occurs prior to less than 20.0 weeks post-LMP.
Time frame: Up to 10,5 years
Number of stillbirth
stillbirth is defined as non-deliberate fetal death anytime in gestation at or after 20 weeks post-LMP.
Time frame: Up to 10,5 years
Number of elective termination
elective termination/abortion is defined as deliberate termination of pregnancy at any time in gestation. Reasons for elective abortions are captured and are classified as due to medical reasons or social reasons.
Time frame: Up to 10,5 years
Number of premature delivery
premature delivery is defined as live birth prior to 37.0 weeks gestation as counted from LMP (or calculated from first-trimester ultrasound-derived due date if last menstrual period uncertain or more than 1 week discrepant). Elective caesarian deliveries or inductions prior to 37.0 completed weeks will be considered separately.
Time frame: Up to 10,5 years
Number of preeclampsia / eclampsia
preeclampsia or eclampsia reported by maternal interview with confirmation in medical record or report by medical record only is captured. Preeclampsia is defined as a new onset of hypertension and proteinuria during pregnancy or postpartum. Eclampsia is the new onset of seizures or coma in a pregnant woman with preeclampsia. These seizures are not related to an existing brain condition.
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Time frame: Up to 1 10,5 years
Pattern of 3 or more minor structural defects
A minor structural defect is defined as a defect which has neither cosmetic nor functional significance to the child (e.g., complete 2,3 syndactyly of the toes). Minor structural defects will be identified only through the study dysmorphology examination for live born infants using the study-specific checklist.
Time frame: Up to 10,5 years
Small for gestational age
small for gestational age is defined as birth size (weight, length or head circumference) less than or equal to the 10th centile for sex and gestational age using standard pediatric CDC growth curves for full term or preterm infants (CDC, 2000; Olsen et al., 2010).
Time frame: Up to 10,5 years
Postnatal growth small for age at approximately one year of age
postnatal growth deficiency is defined as postnatal size (weight, length or head circumference) less than or equal to the 10th centile for sex and age using National Center for Health Statistics (NCHS) pediatric growth curves, and adjusted postnatal age for premature infants if the postnatal measurement is obtained at less than one year of age (CDC, 2000).
Time frame: Up to 10,5 years
Developmental performance at approximately one year of age
Screening of Developmental Milestones: one or more domains scored as abnormal on the Ages and Stages Questionnaire completed by the mother when the infant is approximately one year of age will define achievement of developmental milestones.
Time frame: Up to 10,5 years
Serious or opportunistic infections in the first year of life
serious or opportunistic infections are defined as any one or more diagnoses of tuberculosis, x-ray proven pneumonia, neonatal sepsis, meningitis, bacteremia, invasive fungal infection, pneumocysitis, septic arthritis, osteomyelitis, abcess (deep tissue), and infections requiring hospitalization identified in live born infants up to one year of age.
Time frame: Up to 10,5 years