This study was approved by the Cooper Health System Institutional Research Board. Women diagnosed with cancer during pregnancy were offered enrollment in a multi center cohort study registered with clinicaltrials.gov NCT02749474 that collects diagnostic and treatment information as well as neonatal well being for this unique cohort of patients. Oncologists provided diagnostic and treatment details including the maternal body surface area (BSA), chemotherapeutic agent, doses, and dates of therapy during pregnancy. Neonatal birthweight, gestational age at delivery, and congenital anomalies were collected. Small for gestational age birthweight, defined as <10%, is documented using Fenton criteria for preterm infants or by World Health Organization (WHO) criteria for term infants. Major birth defects were defined according to the Metropolitan Atlanta Congenital Defects Program (MACDP) code modifications developed by the Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333. To evaluate fetal exposures, women were asked to provide newborn meconium on day one of life if they received chemotherapy during pregnancy. Additionally participants agreed to allow pediatric follow-up from pediatricians at 6 months and annually during the child’s birth month. Screening of the meconium using liquid chromatography-high resolution mass spectrometry (LC-HRMS) was previously described . The newborns exposed to taxanes underwent inspection at birth, and then additional follow-up was requested from pediatricians at 6, 12, 24 and 36 months of age. Annual follow-up is ongoing.
Treatment regimens, dosing, maternal BSA, and timing of first treatment are detailed in Table 1. Mean gestational age at the first chemotherapy treatment 17.1 +/- 3.5 weeks and at the first taxane treatment 27 +/- 5.8 weeks. The mean number of days between last treatment during pregnancy and day of birth was 23 +/- 15 days. Meconium was provided for analysis with blinding with regards to the chemotherapy treatment given during pregnancy. For the 8 infants exposed to taxanes, with confirmed detected in meconium at birth, delivery details and neonatal follow-up are described in Table 2. Annual follow-up was requested from pediatricians including developmental age assessment, meeting of appropriate milestones, percentage for head circumference, height and weight, and the diagnosis of any medical disorders or anomalies diagnosed after birth.
Delivery and Birth Defects: Details of the quantification of paclitaxel and metabolites found in meconium has been previously described . The mean gestational age at delivery was 36.6 + 0.9 weeks, and mean birthweight 2530 + 336g. Three term infants weighed less than the 10th percentile for their gestational age at birth per WHO criteria using gestational age and gender. Two children were noted to have a congenital anomaly at the time of birth. One child was born with a familial autosomal dominant anomaly identical to their affected parent; one child delivered breech was diagnosed with hip dysplasia, a common association with malpresentation. While reviewing pediatric follow-up records, a third child was found to have congenital mitral stenosis during an echocardiogram at age 2 months performed due to the presence of a murmur. There was no significant difference in anomalies for 49 neonates exposed to taxanes in utero after completing anthracycline based chemotherapy compared to 58 exposed to this therapy without the addition of taxanes for breast cancer, p=0.29.
Well being: Median age at most recent pediatric evaluation is 18.7 + 9.3 months. All children are meeting age appropriate milestones and none have been diagnosed with major medical disorders aside from typical childhood illnesses such as otitis media, eczema, anemia, and sinusitis.