Maternal exposure to environmental agents during pregnancy

Research so far include:

  • Dietary exposure to N-nitroso compounds [Rice et al., 1989; Kuijten, 1990; McCredie, 1994; Peters, 1994; Preston-Martin, 1996; Blot et al, 1999; Bunin GR, 2000; Pogoda & Preston-Martin, 2001; Huncharek, 2004]
  • Dietary exposure to bioflavonoids [Ross, 1994; Ross, 1996; Spector, 2005]
  • Dietary or direct exposure to diethylstilbestrol (DES) [Herbst, 1971, 1977, 1981, 1999; Gill, 1976, 1977; Depue, 1983; Niculescu, 1985; Anderson, 2000]
  • Tobacco smoking, alcohol consumption and recreational use of drugs by parents [Sasco & Vainio, 1999; Little, 1999]
  • Anemia [Roman, 2005;UKCCS]
  • Infections [Smith, 1997, 1998; Magrath et all., 2013]
  • Intrauterine growth and pregnancy events [O'Neill, Bunch & Murphy, 2012; Musselman et al., 2013]
  • Genital herpes, blood and immunological disorders during pregnancy [Oksuzyan, Crespi, Cockburn, Mezei & Kheifets, 2013]

Dietary exposure to N-nitroso compounds

Animal studies have shown that N-nitroso compounds are powerful carcinogens to be able to pass placenta to the developing fetus. They are considered to be risk factors for certain adult cancers. It is hypothesised that these compounds synthesised from relevant food stuffs (e.g., excessive hot dog and cured meat consumptions) ingested by mothers during pregnancy might act as carcinogens passing through the placenta and that a high intake of fruit and vegetables or vitamin C supplements may play protective roles. This hypothesis has been tested in a number of studies focused on childhood brain tumours. The studies reported an association between these compounds during pregnancy and subsequent childhood brain tumour in offspring. It is also implied in childhood leukaemia.

Dietary exposure to bioflavonoids

Flavonoids, referred as bioflavonoid in media, are commonly known for their antioxidant activity. Good dietary sources of flavonoids include all citrus fruits, berries, onions, parsley, green tea, red wine and dark chocolate. Some of these flavonoids, known as DNA topoisomerase (DNAt2) inhibitors, have been shown to cause site-specific DNA cleavage in the MLL gene breakpoint cluster region on chromosome 11q23. It has been, therefore hypothesised that the infant leukaemias (of which 80% have the MLL abnormality) may occur as a result of maternal exposure to flavonoids in diet during pregnancy and medications that inhibit DNAt2. Contradictory associations have been reported in various studies.

Dietary or direct exposure to diethylstilbestrol (DES)

DES is a synthetic non-steroidal oestrogen drug that was first synthesized in 1938. In 1971, it was found to be a teratogen (refers to disfiguring birth defects or malformation) when given to pregnant women. During the 1960s, DES was used as a growth hormone in the beef and poultry industry. It was later found to cause cancer and was phased out in the late 1970s. Studies demonstrated that cancer could be induced by DES passing through the placenta. Another study found that DES could be trans-generational meaning that the third generation may be effected by the DES used by the maternal grandmother.

Tobacco smoking, alcohol consumption and recreational use of drugs by parents

Animal studies provided evidence that some genotoxic and carcinogenic compounds can pass placenta to the developing fetus. Because of this it is hypothesised that exposure to these agents during pregnancy is a risk factor for childhood cancers. However, no consistent associations were reported between maternal exposures to these agents and childhood cancers.

Studies did not find any consistent association between maternal tobacco smoking during pregnancy and any type of childhood cancer. Possible association has been reported between paternal smoking and ALL. Positive association has been reported between maternal alcohol consumption during pregnancy and AML.

Anemia

It has been reported that there is an increased risk for AML with anemia detected during pregnancy. It has been also reported that anemia should be examined along with other factors.

Infections

ALL has been attributed to an infectious exposure of the fetus during the pregnancy but no evidence has been found to support this theory.

It is reported that low-income and middle-income countries have younger populations and therefore a larger proportion of children with cancer than high-income countries. Also, chronic infections, which remain the most common causes of disease-related death in all except high-income countries, can also be major risk factors for childhood cancer in poorer regions.

Intrauterine growth and pregnancy events

A series of reports illustrate a convincing link between the rate of intrauterine growth and the risk of childhood leukemia. Some studies suggest that this risk relationship also extends to non-Hodgkin lymphoma in children, although, overall, the association with childhood lymphoma is less clear.

It is reported that risk of hepatoblastoma was significantly associated with maternal first trimester weight gain and nearly significantly with maternal multivitamin use. Hepatoblastoma was not associated with other maternal weight changes, maternal illness or medication use during pregnancy.

Genital herpes, blood and immunological disorders

It is suggested that maternal genital herpes, blood and immunological disorders during pregnancy and newborn CNS abnormalities were associated with increased risk of CNS tumors. Maternal infections during pregnancy were associated with decreased risk of CNS tumors. Advanced maternal and paternal ages may be associated with a slightly increased risk of CNS tumors. Factors associated with CNS tumor subtypes varied by subtype, an indicator of different etiology for different subtypes