**4. Results**

### *4.1. Description of the Population*

A total of 115,112 births were recorded during the study period 2008–2011. After exclusion of all birth with unknown birth weight, gestational age, with birth weights less or 500 g, we counted 110,746 singleton births (about 3.8% of the total births were excluded). When, we excluded also newborn without address (about 4.9%); the total singleton births include in the study is 105,346. Among them, 4871 births occurred before 37weeks of pregnancy. The rate of PTB in Paris was 4.6% overall during the study period (2008–2011). Figure 1A shows that low PTB rates, below 3%, are concentrated in the west-central part of Paris while in the north eastern areas, the PTB rate reaches 6 −15%. The geographical pattern of socioeconomic deprivation index is readily observed: the wealthiest census blocks are located in the western part of Paris while the most socioeconomically deprived neighborhoods are located in the northeast and along the perimeter (much trafficked highway) of Paris (Figure 1B). During study period, the PTB rate among women living in deprived census blocks is 4.9% (*n* = 241) compared to 3.18% (*n* = 155) among women living in less deprived census blocks (Significant Kruskal-Wallis test: *p*-value < 0.0001).

**Figure 1.** *Cont*.

**Figure 1.** (**A**): Spatial distribution of crude preterm birth rate in census block areas within Paris; (**B**): Spatial distribution of socio-economic deprivation index in census block areas within Paris; (**C**): Spatial distribution of NO2 average concentrations from 2008 to 2011 in census block areas within Paris.

All the census blocks have an annual average concentration of NO2 over the study period 2008–2011 higher than the European limit fixed to 40 μg/m3. The spatial distribution of the NO2 concentrations reveals a clear gradient from the north-western part of the city (the highest concentrations level >55.8 μg/m3) to the south-east part (the lowest concentrations level <50.6 μg/m3) (Figure 1C).

### *4.2. Neighborhood Socio-Economic Deprivation, NO2 Ambient Air Concentrations and Spatial Distribution of PTB in Paris*

Figure 2 highlights the census blocks including in the most likely clusters of high risk of PTB, their location and spatial shift of centroids from unadjusted clusters to covariate-adjusted clusters. Table 1 summarizes the results of the spatial analyses: the most likely clusters, the number of census blocks, radius and relative risks (RR, the ratio of the observed- to-expected number in each census blocks estimated by SaTScan) for each cluster.


**Table 1.** Summary statistics of the most likely clusters of preterm birth risk and spatial relocation resulting from the adjustment analysis.

RR: relative risk; LLr: log likelihood ratio; a Unadjusted analysis, to identify and localize the most likely cluster(s) of high risk of PTB; b Adjusted analysis for (1) NO2 concentration, (2) socio-economic deprivation index, (3) NO2 concentration and socio-economic deprivation index; c Socio-economic deprivation index.

Unadjusted analysis (Figure 2A) reveals that the most likely cluster is located in the northeast part of Paris. Within the cluster, the risk of PTB is 1.15 times greater than in the rest of the study area (*p*-value < 0.06; Table 1). A total of 169 census blocks composes this most likely cluster, corresponding to about 25,503 inhabitants. The secondary cluster detected is not statistically significant (*p*-value = 0.89).

After adjustment for NO2 concentrations (Figure 2B), the most likely significant cluster is reduced (the radius decreases) and hosts 17 census blocks and 2,814 inhabitants. The risk of PTB increases in comparison with the crude estimate (RR = 1.40, *p*-value = 0.08). The centroid of the cluster shifts and the likelihood ratio slightly decreases from 9.23 (crude model) to 8.84 (adjusted model on air pollution) (Table 1), which suggests that the spatial distribution of NO2 concentrations partially explain the excess risk of PTB observed in the unadjusted analysis.

After adjustment for socio-economic deprivation (Figure 2C), the most likely significant cluster shifts in South-Eastern Paris and the radius substantially decreases in size as well as the likelihood ratio (from 9.23 in the unadjusted model to 5.42) (Table 1). The remaining excess risk becomes not significant (RR = 1.34, *p*-value = 0.8). This indicates that socioeconomic deprivation explains a grea<sup>t</sup> part of the excess risk of PTB observed in the unadjusted analysis.

After joint adjustment for socioeconomic deprivation index and NO2 concentrations: the most likely cluster totally disappears. The likelihood ratio falls from 9.23 to 4.76; we also observed a likelihood ratio decrease when comparing with the model adjusted for socioeconomic deprivation index only (Table 1). The most likely cluster is not significant and located in the same zone in South-Eastern Paris (RR = 1.32; *p*-value = 0.97). This result indicates that the excess risk of PTB detected

from the unadjusted analysis is entirely explained, by the spatial distribution of NO2 concentrations and socioeconomic deprivation.

In our study, the major finding is that while adjustment for socioeconomic deprivation level was the essential variable explaining the most likely cluster (as shown in Table 1), further adjustment for NO2 concentrations reduces the LLR to a larger degree than that obtained in the model with socioeconomic deprivation level alone or with the NO2 concentrations alone.

**Figure 2.** Spatial relocation of the most likely cluster of unadjusted PTB risk (**A**); after adjustment for NO2 exposure (**B**); after adjustment for NO2 exposure and socio-economic level (**C**). Legend: the dark area represents the census blocks included in the most likely cluster of high risk of PTB.
