Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P
Bonferroni
< 1.06 x 10
−7
). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914,
p
= 6.12 x 10
−74
) and BMI in pregnancy (3/914,
p
= 1.13x10
−3
), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
As the incidence of cancer in pregnancy has been increasing in recent decades, more specialists are confronted with a complex oncologic–obstetric decision-making process. With the establishment of (inter)national registries, including the International Network on Cancer, Infertility and Pregnancy, and an increasing number of smaller cohort studies, more evidence on the management of cancer during pregnancy is available. As fetal, neonatal, and short-term pediatric outcomes after cancer treatment are reassuring, more women receive treatment during pregnancy. Prenatal treatment should adhere to standard treatment as much as possible to optimize maternal prognosis, always taking into account fetal well-being. In order to guarantee the optimal treatment for both mother and child, a multidisciplinary team of specialists with expertise should be involved. Apart from oncologic treatment, a well-considered obstetric and perinatal management plan discussed with the future parents is crucial. Results of non-invasive prenatal testing are inconclusive in women with cancer and alternatives for prenatal anomaly screening should be used. Especially in women treated with chemotherapy, serial ultrasounds are strongly recommended to follow-up fetal growth and cervical length. After birth, a neonatal assessment allows the identification of any cancer or treatment-related adverse events. In addition, placental histologic examination aims to assess the fetal risk of metastasis, especially in women with malignant melanoma or metastatic disease. Breastfeeding is discouraged when systemic treatment needs to be continued after birth. At least a 3-week interval between the last treatment and nursing is recommended to prevent any treatment-induced neonatal effects from most non-platinum chemotherapeutic agents.
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