Reference intervals for hemoglobin and hematocrit in a low-risk pregnancy cohort: implications of racial differences

<p><b>Objective:</b> As anemia in pregnancy is associated with adverse perinatal outcomes, we sought to define the mean and the fifth percentile of Hb and Ht using a contemporary multiethnic large cohort of low-risk pregnancies, and assess potential racial differences.</p> <p><b>Methods:</b> We conducted a retrospective cohort study on women who delivered between 1 January 2008 and 31 December 2013 in Reggio Emilia County, Italy. Linear mixed effects models were used to describe changes in mean Hb and Ht, while quantile regression with matrix-design bootstrap defined changes in the fifth percentile of Hb and Ht, controlling for race, maternal age, smoking, and pregnancy number.</p> <p><b>Results:</b> We analyzed 23,657 hemograms from 7318 pregnancies and 6870 women. Multivariate analysis showed that when compared to Caucasians’, African women’s mean Hb and Ht were respectively 0.24 (95%CI 0.3–0.17) g/dl and 0.7 (95%CI 0.8–0.5) % lower, while Asian mothers’ were 0.11 (95%CI 0.19–0.03) g/dl and 0.3 (95%CI 0.5–0.1) % inferior. Similarly, both African and Asian women had lower fifth Ht percentiles (−1, 95%CI −1.3 to −0.6, and −0.4, 95%CI −0.7 to −0.04) than Caucasians, while African mothers also had lower fifth Hb percentile (0.3, 95%CI 0.5–0.1). The fifth percentile for Hb and Ht were, respectively, 11.3 (95%CI 11–11.5) g/dl and 32.8 (95%CI 32.3–33.4) % in the first trimester, 10.4 (95%CI 10.1–10.6) g/dl and 30.2 (95%CI 29.6–30.8) % in the second trimester, 10.1 (95%CI 9.8–10.3) g/dl and 30.6 (95%CI 30–31.1) % in the third trimester.</p> <p><b>Conclusions:</b> We provided contemporary references to define anemia in pregnancy, and we confirmed that even in pregnancy, African and Asian women have lower Hb and Ht than Caucasian. Racial and population-specific references may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment.</p

Altered Cortical Cell Counts in 6 Month Old Offspring Brain.

<p>Nissl staining of neocortex of 6 month old mice offspring shown here at 40 X magnification in panels A (male) and C (female). Neurons were identified by dark-blue positive staining. Glial cells were smaller than neurons and had darker nuclei but no clearly visible Nissl bodies in the cytoplasm. A decrease in positive staining is seen male and female sFlt-1 offspring (A: sFlt-1, C: sFlt-1) when compared to controls (A: mFc, C: mFc) and pravastatin treatment group offspring (A: sFlt-1-pra, C: sFlt-1-pra). Total cell count as well as neuronal and glial cell counts were performed on randomly chosen 7-8 fields in the frontal cortex per animal and analyzed by 2-way ANOVA (n = 3 for all groups by gender). Data are reported as mean ± SEM. Male data are seen in Panel B, and female data in Panel D. Significant decreases in total cell count are seen in both male and female sFlt-1 offspring when compared to controls (p<0.0001) and sFlt-1-pra (male and female p<0.0001), though the female sFlt-1-pra group remained significantly different from mFc controls (p = 0.001). There is no difference in glial cell count between all three groups. Neuronal cell count appears to drive this total cell count difference. The male sFlt-1 offspring (B) show a significant decrease in neurons when compared to mFc controls (p = 0.0003) and sFlt-1-pra offspring (p = 0.001). Female sFlt-1 offspring (D) show a similar drop in neuronal count versus mFc controls and sFlt-1-pra offspring (p<0.0001), with pravastatin-exposed offspring remain significantly different from mFc controls (p = 0.03).</p

Magnetic Resonance Images of 6 Month Old Offspring Brains.

<p>Three-dimensional T2-weighted images of whole brain were obtained using a vertical bore 11.7 Tesla MRI scanner. Here in these representative coronal slices, the ventricles and periventricular tissue of male (A) and female (B) offspring are outlined in coronal view, allowing comparison between treatment groups. A decrease in ventricular volume was seen in male sFlt-1 offspring (A: sFlt-1) when compared to controls (A: mFc). Pravastatin exposure (A: sFlt-1-pra) reversed this effect. An opposite trend was seen in the female sFlt-1 offspring brain (B: sFlt-1) when compared to control (B: mFc) and pravastatin-treatment offspring (B: sFlt-1-pra). Nissl staining of coronal sections at a single ventricle and its periventricular tissue in adult offspring brains at 40 X magnification is shown in panels C and D. In these representative images, male offspring showed a decrease in volume in sFlt-1 (C: sFlt-1) offspring when compared to control (C: mFc). In-utero pravastatin exposed male offspring (C: sFlt-1-pra) showed normalization of ventricular shape and size. An increase in ventricular volume is seen in female sFlt-1 offspring brains (D: sFlt-1) when compared to control (D: mFc). Though complete resolution is not seen, there is improvement in ventricle size in the pravastatin-exposed female offspring (D: sFlt-1-pra). These representative images correlate with MRI volumetric data for male (E: mFc (n = 9), sFlt-1 (n = 3), sFlt-1-pra (n = 6)) and female (F: mFc (n = 6), sFlt-1 (n = 3), sFlt-1-pra (n = 10)) offspring brains as analyzed by 1-way ANOVA. The male sFlt-1 offspring had significantly decreased volume when compared to mFc controls and the pravastatin treatment group in males (E: p = 0.02), whereas the opposite effect was seen in female offspring (F: p<0.05).</p

Altered Brain Volumes in 6 Month Old Female Offspring Brain.

<p>Regions of interest were analyzed by 1-way ANOVA in 6 month old female mice offspring born to pregnant CD1 mice injected either with an adenovirus carrying sFlt-1 or adenovirus carrying mFc fragment. Mice injected with sFlt-1 were treated with either pravastatin or water to result in three groups of offspring animals: mFc (n = 6), sFlt-1 (n = 3), and sFlt-1-pra (n = 10). Data are reported as mean ± SEM. The sFlt-1 group offspring showed decreased volumes at the inferior colliculus (A; p = 0.04), thalamus (B; p<0.0001), and lateral globus pallidus (C; p = 0.02) when compared to the mFc control offspring. Increased volumes were seen at the stria medullaris (D; p = 0.01), and fasciculus retroflexus (E; p = 0.01). The overall ameliorative effect of pravastatin exposure in utero is seen. Not shown are brain regions with similar volumes between groups.</p

Regions of Interest Imaged Via MRI in the Brains of 6-Month Old Male and Female Offspring.

<p>Regions of Interest Imaged Via MRI in the Brains of 6-Month Old Male and Female Offspring.</p

Functions of Brain Regions with Significant Volume Changes Seen in MRI Imaging of Adult Mouse Brains.

<p>Functions of Brain Regions with Significant Volume Changes Seen in MRI Imaging of Adult Mouse Brains.</p