Although air pollution differs around the world, it is a global threat having a significant impact on human health and ecosystems. The World Health Organization (WHO) has proposed limits for the concentration of key air pollutants, but these are often not identical to national standards [1]. Exposure to ambient air pollution increases mortality and morbidity and shortens life expectancy. Environmental air pollution caused 4.2 million premature deaths in 2016 [1]. Pollutants derive from a wide range of sources, like agricultural activities, energy production and distribution, road transport, waste, fuel combustion, and natural phenomena [2]. The key air pollutants are particulate matter—black carbon, ozone, and nitrogen oxides—(PM), carbon monoxide (CO), sulphur dioxide (SO${}_2$), and nitrogen dioxide (NO${}_2$). These pollutants are responsible for an increase in life-threatening conditions, such as lung cancer, cerebrovascular accidents, cardiovascular conditions, and chronic obstructive pulmonary disease (COPD) [3].

Exposure to air pollution during pregnancy is associated with adverse birth outcomes [4]. These adverse birth outcomes include preterm birth, low birth weight and hypertensive disorders in pregnancy. Specifically increase in exposure during the first and second trimester increases the risks on pre-eclampsia [5]. Exposure to air during pregnancy pollution also has negative effects on offspring. Maternal exposure during whole pregnancy is associated with increased risks for neonatal respiratory complications, such as respiratory distress, asphyxia and transient tachypnoea [6]. Even exposure to air pollution prior to conception is associated with an increased risk for preterm birth and low birth weight [4].

Unfortunately, the relationship between reducing pollution and improving health is not straightforward. The majority of studies on pollution and health are correlational and not etiological. A recent Cochrane review studied the effectiveness of interventions in reducing environmental air pollution and improving health. Evidence regarding the improvement of health outcomes for all intervention categories has been either weak or very weak certainty [7].

In this paper, we first present a short overview of the health issues related to air pollution in the general population, allowing comments on differences in the pregnancy cases that we discuss in more detail in the following paragraph.

The literature correlating health effects with air pollution is overwhelming. For the ease of the overview, we will consecutively discuss particulate matter, black carbon, ozone, and nitrogen oxides. Our discussion will cover mainly the respiratory and vascular effects, as these systems are most relevant during pregnancy to fetal growth and development. We will not discuss the endocrine-disrupting effects as these have recently been reviewed by Darbre [8].

2.1 Particulate matter

Particulate matter is the collective term to identify the mixture of solid particles and liquid droplets in air. PM derives from human (i.e., non-exhaust emission sources, brake ware emissions, exhaust emission sources, and industrial emissions) as well as non-human (i.e., windblown dust, sea salt aerosols, biological aerosols, and volcanic eruptions) sources [9]. These particles exist in different sizes and shapes. Size is linked to their potential for causing distinct health problems (Fig. 1). Most research examines particulate matter with aerodynamic diameter below 10 $\mu$m (also referred to as PM${}_{10}$) or below 2.5 $\mu$m (also referred to as PM${}_{2.5}$). Although PM${}_{10}$ can easily enter the lungs and bloodstream, PM${}_{2.5}$ is more hazardous. Due to its small size, it penetrates even deeper into the lungs with ease (Fig. 1).

Fig. 1.

Penetration of particulate matter in the respiratory system.

Exposure to PM increases plasma viscosity and serum fibrinogen concentration and leads to systemic inflammation. Inhalation of diesel exhaust triggers an acute endothelin-1 release causing vasoconstriction. Short term exposure also induces vascular injury and depletion of circulating endothelial progenitor cells [10].

Hamanaka & Mutlu [11] revealed in their review that PM is a major contributor to cardiovascular morbidity and mortality. The exact contribution is not completely understood because exposure to particulate matter is also linked with effects on other systems than the cardiovascular system. A large prospective cohort study of Yusuf et al. [12] in 21 countries estimated that ambient air pollution was responsible for 13.9% of cardiovascular disease cases. Exposure was higher in middle-income countries and highest in low-income countries.

Evidence suggests not only an association but a causal relationship because an improvement in air quality is associated with public health benefits [13].

There is an association between exposure to ambient air pollution and respiratory diseases like asthma, COPD, decreased pulmonary function, and lung cancer [14]. Interventions to reduce exposure to particulate matter (closure of factories, coal bans, exchange of stoves, wood-burning bans, diesel vehicle bans, or high vehicle standards) have led to improvements in respiratory health [7].

Several specific reviews have been published on the impact of air pollution on particular pregnancy outcomes such as fetal growth restriction, pre-eclampsia or congenital anomalies: in this text we want to offer a more general overview not limited to a single perinatal problem [20, 22].

We will discuss the respiratory cardiovascular and other effects of air pollution in pregnant women. We will compare these effects to those known in a non-pregnant population. Next, we will focus on specific gestation-related issues, namely fetal growth restriction and preterm birth. We will not elaborate on such issues as congenital malformations, as these have recently been reviewed in several studies [19, 20].

In a normal pregnancy, extensive maternal cardiovascular changes occur within the first 6 weeks after conception. There is a reduction of the maternal blood pressure, a decrease in peripheral vascular resistance, and a buildup of the cardiac output from the start of the pregnancy until mid-pregnancy, resulting in a 40% increase [23]. Also, there is a progressive increase in heart rate and stroke volume as a result of the augmentation of venous return, secondary to the expansion of the plasma volume. All these cardiovascular adaptations will return to pre-pregnancy levels 6 weeks after delivery [24].

PM${}_{2.5}$, PM${}_{10}$, NO${}_2$, CO, and O${}_3$ have negative effects on these maternal cardiovascular adaptations. The effect of these air pollutants on fertility, birth weight, preterm birth, and the presence of congenital anomalies was investigated (Table 1, Ref. [3, 20, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40]: Summary of the effects of air pollution on pregnancy) [25].

In the present review we attempted to give a concise overview of the current data, based on published studies, of the effects of different pollutants on pregnant mothers and their fetuses.

Although the relationship between cleaner air and better outcome of health feels very natural, a recent Cochrane review failed to demonstrate any significant effect between air-cleaning activities and health.

This counterintuitive conclusion could partly be caused by differences between measurement methodology differing greatly between studies. Some of the techniques were not available in the research group or, at the moment of the study, were not even invented.

Since some of the effects of air pollution can be linked to the interaction with chemical or molecular reactions inside the human body, genetic predisposition potentially influences the expression levels/post-translational modifications and/or epigenetics of these specific cellular proteins leading to completely different reaction patterns. As we are not all similarly sensitive to the effects of alcohol consumption, it could be hypothesized that some people are genetically more or less sensitive to specific air pollutants, making large-scale epidemiological studies very difficult to interpret and care should be taken to draw conclusions just looking at epidemiological data without understanding the biological basis.

For some factors, it is not very clear whether there is a linear relationship between the concentration of the pollutant and the health effects. It could logically be hypothesized that pollutants only play an effect from a specific threshold level upwards.

The idea of personal sensitivity and genetic/epigenetic effect warrants new and more detailed studies to unravel the mechanisms responsible for these adverse effects and to finally understand the individual risks leading to better guidelines and recommendations.

In addition, in future published studies, we propose to clearly define and specify the precise methodology used and correct levels of the different pollutants for the different outcome parameters making future reviews more reliable.

There are multiple conflicting factors involved in studying the effect of pollution on pregnancy outcomes. Often people that live in areas with high pollution, are of lower socio-economic class, have access to less and lower quality medical care, are overweight, more likely to smoke, have exposure to pealing and lead paint in their homes. All of which could increase pregnancy and neonatal complications and often go uncontrolled for in studies. Future studies should seek to isolate the effect of pollutants on pregnancy outcome, the final analysis should correct for covariates such as socio-economic class, access to medical care, obesity, smoking habits and household exposure to lead and other domestic pollutants. Although, a relationship between pollution exposure and pregnancy complications seems self-evidence, further rigorous studies are required.

The best and most widely studied pollutants are PM${}_{2.5}$.

PM${}_{2.5}$, however, is made up of varying compositions of different substances, including BC.

This makes comparing PM${}_{2.5}$ levels unreliable. We propose to study BC instead because exposure to PM${}_{2.5}$ has a negative effect on fertility. It induces an increased plasma viscosity and fibrinogen level in the mother, leading to systemic inflammation. Elevated levels of PM${}_{2.5}$ are also responsible for cardiovascular maladaptation.

Forthcoming studies should analyze and discuss the dose relationship between the pollutants and aim to establish a threshold above which problems can be expected.

LVdE performed the research. GL designed the figures, DM and YJ provided advice and critical reading of the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Not applicable.

We would like to express gratitude to all those who helped during the writing of the manuscript.

This research received no external funding.

The authors declare no conflict of interest.