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. 2018 Jan 15;8(1):791.
doi: 10.1038/s41598-017-19133-9.

Placental Morphology Is Associated with Maternal Depressive Symptoms during Pregnancy and Toddler Psychiatric Problems

Marius Lahti-Pulkkinen  1   2   3 , Melissa Jane Cudmore  4 , Eva Haeussner  5 , Christoph Schmitz  5 , Anu-Katriina Pesonen  6 , Esa Hämäläinen  7 , Pia M Villa  8 , Susanna Mehtälä  9 , Eero Kajantie  10   11   12 , Hannele Laivuori  9   13   14   15 , Rebecca M Reynolds  4 , Hans-Georg Frank  5 , Katri Räikkönen  6
Affiliations

Placental Morphology Is Associated with Maternal Depressive Symptoms during Pregnancy and Toddler Psychiatric Problems

Marius Lahti-Pulkkinen et al. Sci Rep. .

Abstract

Maternal depressive symptoms during pregnancy predict increased psychiatric problems in children. The underlying biological mechanisms remain unclear. Hence, we examined whether alterations in the morphology of 88 term placentas were associated with maternal depressive symptoms during pregnancy and psychiatric problems in 1.9-3.1-years old (Mean = 2.1 years) toddlers. Maternal depressive symptoms were rated biweekly during pregnancy with the Center of Epidemiological Studies Depression Scale (n = 86). Toddler psychiatric problems were mother-rated with the Child Behavior Checklist (n = 60). We found that higher maternal depressive symptoms throughout pregnancy [B = -0.24 Standard Deviation (SD) units: 95% Confidence Interval (CI) = -0.46; -0.03: P = 0.03; Mean difference = -0.66 SDs; 95% CI = -0.08; -1.23: P = 0.03; between those with and without clinically relevant depressive symptoms] were associated with lower variability in the placental villous barrier thickness of γ-smooth muscle actin-negative villi. This placental morphological change predicted higher total (B = -0.34 SDs: 95% CI = -0.60; -0.07: P = 0.01) and internalizing (B = -0.32 SDs: 95% CI = -0.56; -0.08: P = 0.01) psychiatric problems in toddlers. To conclude, our findings suggest that both maternal depressive symptoms during pregnancy and toddler psychiatric problems may be associated with lower variability in the villous membrane thickness of peripheral villi in term placentas. This lower heterogeneity may compromise materno-fetal exchange, suggesting a possible role for altered placental morphology in the fetal programming of mental disorders.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
(A) Maternal clinically significant antenatal depressive symptoms and placental SMA-negative villi villous barrier thickness variability. The figure shows the unadjusted mean values and 95% Confidence Intervals of the standard deviation of placental SMA-negative villi villous barrier thickness (in standard deviation units) for mothers with trimester-weighted mean antenatal depressive symptoms below or above the clinical cutoff of ≥16 points. P-values refer to group difference significances from unadjusted linear regression models (model 1), models adjusted for maternal age, education, pre-pregnancy BMI, hypertensive and diabetic disorders in pregnancy and gestation length (model 2), and models adjusted also for maternal history of physician-diagnosed mental disorders before pregnancy (model 3). (B) Maternal accumulative depressive symptoms during pregnancy and SMA-negative villi villous barrier thickness variability. The figure shows the unadjusted mean values and 95% Confidence Intervals of the standard deviation of SMA-negative villi villous barrier thickness in standard deviation units, according to the number of pregnancy trimesters [0, 1, 2–3] maternal depressive symptom scores during pregnancy were above the clinical cutoff of ≥16, when calculated from the value at the first trimester and mean values across second and third trimesters. P-values refer to the significances of group differences and linear trends from unadjusted linear regression models (model 1), models adjusted for maternal age, education, pre-pregnancy BMI, hypertensive and diabetic disorders in pregnancy and gestation length (model 2), and models adjusted also for maternal history of physician-diagnosed mental disorders before pregnancy (model 3).
Figure 2
Figure 2
Immunohistochemical double labeling of perivascular sheath and fetal villous endothelium. (A) Shows an example of a γ-smooth-muscle-actin(SMA)-positive villus (indigo-blue in perivascular position; white arrows). The endothelium of fetal vessels is labelled (CD34: brown; black arrows), the villous stroma marked by asterisks and the trophoblast (bluish nuclei; shaded arrows) visible. (B) Exemplifies a SMA-negative villus (no SMA reactivity in perivascular position). The endothelium of fetal vessels is labelled (CD34: brown; black arrows), villous stroma marked by asterisks and trophoblast (bluish nuclei; shaded arrows) visible. Red arrow heads label vasculo-syncytial-membrane spots. (A) Scale bar is 25 µm and valid for (B).
Figure 3
Figure 3
An illustration of the villous membrane thickness measurement principle. (A,B) Show examples of SMA-negative villi with endothelium labelled by CD34-reactivity (brown reaction product). (C,D) Show examples of SMA-positive villi (indigo-blue reaction product in perivascular position) with endothelium labelled by CD34-reactivity (brown reaction product). (A–D) We measured membrane thickness with the Nearest Neighbor analysis and the shortest distance (red line) from the trophoblast to the fetal endothelium by increasing a circle (red) from the trophoblast surface until first intersection with the endothelium. Exemplary measurement positions are marked with black arrows. Scale bar is 25 µm.
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