Low birth weight

Low birth weight (LBW) is defined by the World Health Organization as a birth weight of a infant of 2,499 g (5 lb 8.1 oz) or less, regardless of gestational age.[1] Subcategories include very low birth weight (VLBW), which is less than 1,500 g (3 lb 5 oz), and extremely low birth weight (ELBW), which is less than 1,000 g (2 lb 3 oz).[2] Normal weight at term delivery is 2,500–4,200 g (5 lb 8 oz–9 lb 4 oz).

Causes

LBW is either caused by preterm birth (that is, a low gestational age at birth, commonly defined as younger than 37 weeks of gestation) or the infant being small for gestational age (that is, a slow prenatal growth rate), or a combination of both.

In general, risk factors in the mother that may contribute to low birth weight include young ages, multiple pregnancies, previous LBW infants, poor nutrition, heart disease or hypertension, untreated coeliac disease, drug addiction, alcohol abuse, and insufficient prenatal care. It can also be caused by prelabor rupture of membranes.[3] Environmental risk factors include smoking, lead exposure, and other types of air pollutions.[4][5][6]

Preterm birth
Further information: Preterm birth

Four different pathways have been identified that can result in preterm birth and have considerable evidence: precocious fetal endocrine activation, uterine overdistension, decidual bleeding, and intrauterine inflammation/infection.[7] From a practical point a number of factors have been identified that are associated with preterm birth, however, an association does not establish causality.

Being small for gestational age
Further information: Small for gestational age

Being small for gestational age can be constitutional, that is, without an underlying pathological cause, or it can be secondary to intrauterine growth restriction, which, in turn, can be secondary to many possible factors. For example, babies with congenital anomalies or chromosomal abnormalities are often associated with LBW. Problems with the placenta can prevent it from providing adequate oxygen and nutrients to the fetus. Infections during pregnancy that affect the fetus, such as rubella, cytomegalovirus, toxoplasmosis, and syphilis, may also affect the baby's weight.

Environmental factors

While active maternal tobacco smoking has well established adverse perinatal outcomes such as LBW, that mothers who smoke during pregnancy are twice as likely to give birth to low-birth weight infants. Review on the effects of passive maternal smoking, also called environmental tobacco exposure (ETS), demonstrated that increased risks of infants with LBW were more likely to be expected in ETS-exposed mothers.[8][9]

Regarding environmental toxins in pregnancy, elevated blood lead levels in pregnant women, even those well below 10 ug/dL can cause miscarriage, premature birth, and LBW in the offspring. Although 10 ug/dL is the US Centers for Disease Control and Prevention's “level of concern”, this cut-off value still results in significant harm to gestating fetuses.[10]

The combustion products of solid fuel in developing countries can cause many adverse health issues in people. Because a majority of pregnant women in developing countries, where rate of LBW is high, are heavily exposed to indoor air pollution, increased relative risk translates into substantial population attributable risk of 21% of LBW.[11]

The potentially harmful effects of air pollution are particularly concerning given the pervasiveness of air pollution. The exact mechanism by which air pollution affects fetuses is unknown, but it is suggested that air pollutants enter the body through direct diffusion or active transport.[12] Once in the body, it is thought that air pollutants affect birth outcomes by oxidative stress, changes in hemodynamic factors, disruption of endocrine systems, and finally with genetic and epigenetic changes.[13]

One environmental exposure which has been found to increase the risk of low birth weight is particulate matter, a component of ambient air pollution.[14] Because particulate matter is composed of extremely small particles, even nonvisible levels can be inhaled and present harm to the fetus.[15] Particulate matter exposure can cause inflammation, oxidative stress, endocrine disruption, and impaired oxygen transport access to the placenta,[16] all of which are mechanisms for heightening the risk of low birth weight.[17] When inhaled, particles smaller than 1 µm can penetrate the alveolar wall, enter the maternal bloodstream so that particles and inflammatory mediators cross the placenta, and reach the fetus.[18] Some studies have indicated that PM2.5 exposure during the second trimester may lead to the strongest effects on low birth weight.[19] To reduce exposure to particulate matter, pregnant women can monitor the EPA’s Air Quality Index and take personal precautionary measures such as reducing outdoor activity on low quality days, avoiding high-traffic roads/intersections, and/or wearing personal protective equipment (i.e., facial mask of industrial design). Indoor exposure to particulate matter can also be reduced through adequate ventilation, as well as use of clean heating and cooking methods.[20][21]

Other environmental exposures that have been shown to increase the rates of low birth weight are compounds that are associated with traffic-related pollution, most significantly, nitrogen dioxide (NO2). Nitrogen dioxide is often used as an indicator of traffic-related air pollution.[22] Stieb et al. used national data to study the association between nitrogen dioxide exposure and pregnancy outcomes in 2.5 million births in Canada between 1999 and 2008 using land use regression models to estimate nitrogen dioxide concentrations.[22] They found that exposure to nitrogen dioxide was associated with 4% higher odds of giving birth to a child that is small for gestational age.[22] Even after the researchers adjusted for neighborhood socioeconomic factors, there was still a strong association between nitrogen dioxide and low birth weight.[22] This research also showed evidence of a dose-response relationship, meaning that more exposure to nitrogen dioxide an expectant mother was exposed to, the higher the likelihood of giving birth to a low birth weight child.[22]

The association between traffic related pollution and low birth weight has been observed in multiple studies conducted in different parts of the world. Généreux et al. studied a population of Canadian women and found that living close to highways is associated with adverse birth outcomes, even among women considered high socioeconomic status.[23] Ghosh et al. examined 4 air toxin monitoring stations in Los Angeles, California, and found that the odds of a low birth weight child increased by 2-5% when mothers were exposed to nitric oxide, nitrogen dioxide, and nitrogen oxides.[24] Furthermore, these researchers found that traffic exhaust leads to low birth weight in long-term and short-term exposure, especially in the third trimester.[25] In a study of Swedish newborn children, researchers used ultrasound techniques to show that exposure to nitrogen oxides consistently and negatively affected fetal growth late in pregnancy (after 7 months). Furthermore, they found that the population that was affected had relatively low exposures, which were generally below WHO air quality guidelines.[18]

Another measure of air pollution is exposure to polycyclic aromatic hydrocarbons from motor vehicle exhaust, which has been associated with a 1-3% increased odds of low birth weight.[26] It is hypothesized that hydrocarbons, which can cross into the placenta, have antiestrogenic effects and also cause DNA damage that leads to apoptosis or cell death.[27]

A correlation between maternal exposure to CO and low birth weight has been reported that the effect on birth weight of increased ambient CO was as large as the effect of the mother smoking a pack of cigarettes per day during pregnancy.[28] It has been revealed that adverse reproductive effects (e.g., risk for LBW) were correlated with maternal exposure to air pollution combustion emissions in Eastern Europe and North America.[29] Mercury is a known toxic heavy metal that can harm fetal growth and health, and there has been evidence showing that exposure to mercury (via consumption of large oily fish) during pregnancy may be related to higher risks of LBW in the offspring.[30]

It has also been hypothesized that another air pollutant, ozone, can cause low birth weight. While ozone has been associated with preterm delivery, studies linking ozone and low birth weight have been inconsistent.[31] Some have shown a positive association between the two, others have shown no association, and some have found that ozone may actually be a protective factor against low birth weight.[32] This last phenomenon is potentially explained by studies that have shown that ozone can activate an antioxidant system, which may help bring oxygen to tissues.[33]

It was revealed that, exposure of pregnant women to airplane noise was found to be associated with low birth weight. Aircraft noise exposure caused adverse effects on fetal growth leading to low birth weight and preterm infants.[34][35]

The annual low birth weight prevalence in Japan from 2012 onward was associated with the prefecture-specific dose-rate derived from Cs-137 deposition after the Fukushima Nuclear Power Plant accidents in March 2011. One μSv/h (equivalent to 8.8 mSv/year) increases the odds of observing low birth weight events by approximately 10%.[36]

Periodontal health

Low birthweight, pre-term birth and pre-eclampsia have been associated with maternal periodontitis exposure. But the strength of the observed associations is inconsistent and vary according to the population studied, the means of periodontal assessment and the periodontal disease classification employed.[37] However the best is that the risk of low birth weight can be reduced with very simple therapy. Treatment of periodontal disease during gestation period is safe and reduction in inflammatory burden reduces the risk of preterm birth as well as low birth weight.[38]

Effects

LBW is closely associated with fetal and Perinatal mortality and Morbidity, inhibited growth and cognitive development, and chronic diseases later in life. At the population level, the proportion of babies with a LBW is an indicator of a multifaceted public-health problem that includes long-term maternal malnutrition, ill health, hard work and poor health care in pregnancy. On an individual basis, LBW is an important predictor of newborn health and survival and is associated with higher risk of infant and childhood mortality.[39]

Low birth weight constitutes as sixty to eighty percent of the infant mortality rate in developing countries. Infant mortality due to low birth weight is usually directly causal, stemming from other medical complications such as preterm birth, PPROM,[40] poor maternal nutritional status, lack of prenatal care, maternal sickness during pregnancy, and an unhygienic home environment.[41][42] According to an analysis by University of Oregon, reduced brain volume in children is also tied to low birth-weight.[43][44]

Epidemiology
Low birth weight world map (2002)

A study by the Agency for Healthcare Research and Quality (AHRQ) found that of the 3.8 million births that occurred in the United States in 2011, approximately 6.1% (231,900) were diagnosed with low birth weight (<2,500 g). Approximately 49,300 newborns (1.3%) weighed less than 1,500 grams (VLBW).[45] Infants born at low birth weight are at a higher risk for developing neonatal infection.

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