Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes

Authors: CHRISTENSEN, SOPHIE - University Of Copenhagen; ROM, ANE - Rigshospitalet - Copenhagen University Hospital; GREVE, TINE - Hvidovre Hospital; LEWIS, JACK - University Of Copenhagen; FRØKIÆR, HANNE - University Of Copenhagen; Allen, Lindsay - A; MØLGAARD, CHRISTIAN - University Of Copenhagen; RENAULT, KRISTINA - University Of Copenhagen; MICHAELSEN, KIM - University Of Copenhagen

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2023
Publication Date: 9/4/2023
Citation: Christensen, S.H., Rom, A.L., Greve, T., Lewis, J.I., Frøkiær, H., Allen, L.H., Mølgaard, C., Renault, K.M., Michaelsen, K.F. 2023. Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes. Frontiers in Nutrition. https://doi.org/10.3389/fnut.2023.1223753.
DOI: https://doi.org/10.3389/fnut.2023.1223753

Interpretive Summary: Intrauterine and postnatal infant growth can already be affected during pregnancy. Additionally, maternal inflammation and insulin resistance could also affect pregnancy and breastfeeding outcomes and mother's hormones in circulation that transfer into the milk (HM) may influence the infant's appetite and thereby milk intake, but the relationship are less understood. We examined associations between pre-pregnancy body-mass-index (BMI) and gestational inflammation and metabolic markers, and associations between gestational inflammation and metabolic markers and pregnancy and breastfeeding outcomes. Thus, 71 mother-infant pairs participating in the Mothers, Infants and Lactation Quality study were included. Fasting blood samples were collected around 28th gestational week, and HM samples at three time points from 1.0-8.5 months. Total milk intake was measured using 24-hour test weighing. Maternal inflammation and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-a (TNFa), interferon-' (IFN'), Interleukin (IL)-6, IL-8, very-low, low- and high-density lipoprotein (VLDL, LDL, HDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, c-peptide, homeostasis model assessment of insulin resistance (HOMA-IR) as well as glucose concentration at t=120 minutes following an oral glucose tolerance test. IL-6, IL-8, TNFa, IFN', leptin, insulin, and adiponectin were also measured in HM the three postpartum visits. We found that pre-pregnancy BMI was positively associated with concentrations of hs-CRP, log-TNFa, c-peptide, leptin, insulin and HOMA-IR in pregnancy. Further, HDL in pregnancy was inversely associated with gestational age (GA) at birth and birth weight z-score, while triglycerides and glucose(t=120) were positively related with birth weight z-score. Both hs-CRP, VLDL and triglycerides were positively associated with placental weight. HDL, insulin, leptin and HOMA-IR were positively related with duration of exclusive breastfeeding (EBF). Lastly, insulin and HOMA-IR in pregnancy were negatively associated with milk intake, but only between 1.0-3.49 months postpartum. In conclusion, pre-pregnancy BMI was associated with some markers of inflammation and metabolic function during pregnancy. Interestingly, a few of these markers were further associated with higher placental weight, higher birth weight z-score, lower milk intake and longer duration of EBF. Thus, overweight prior to pregnancy may affect breastfeeding and thereby possibly the infant.

Technical Abstract: Programming in utero influence intrauterine and postnatal infant growth, and a few studies indicate that maternal inflammation and insulin resistance might affect pregnancy and breastfeeding outcomes. Furthermore, hormones identified in maternal circulation and in human milk (HM) may influence appetite-regulation and thereby milk intake, but the associations are less understood. To investigate associations between pre-pregnancy body-mass-index (BMI) and gestational inflammation and metabolic markers and associations between gestational inflammation and metabolic markers and pregnancy and breastfeeding outcomes, respectively. Seventy-one mother-infant dyads participating in the Mothers, Infants and Lactation Quality study were included in the present study. Fasting blood samples were collected around 28th gestational week, whereas HM samples were collected at three time points from 1.0-8.5 months, where total milk intake was additionally assessed using 24-hour test weighing. Maternal inflammation and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-a (TNFa), interferon-' (IFN'), Interleukin (IL)-6, IL-8, very-low, low- and high-density lipoprotein (VLDL, LDL, HDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, c-peptide, homeostasis model assessment of insulin resistance (HOMA-IR) as well as glucose concentration at t=120 minutes following an oral glucose tolerance test. Of these, IL-6, IL-8, TNFa, IFN', leptin, insulin, and adiponectin were also measured in HM the three postpartum visits. Pre-pregnancy BMI was positively associated with concentrations of hs-CRP, log-TNFa, c-peptide, leptin, insulin and HOMA-IR in pregnancy. Secondly, HDL in pregnancy was inversely associated with gestational age (GA) at birth and birth weight z-score, whereas triglycerides and glucose(t=120) were positively associated with birth weight z-score. Both hs-CRP, VLDL and triglycerides were positively associated with placental weight. Furthermore, HDL, insulin, leptin and HOMA-IR were positively associated with duration of exclusive breastfeeding (EBF). Lastly, insulin and HOMA-IR in pregnancy were negatively associated with milk intake, but only between 1.0-3.49 months postpartum and not at later time points. Pre-pregnancy BMI was associated with certain markers of inflammation and metabolic function during pregnancy. Interestingly, a few of these markers were further associated with higher placental weight, higher birth weight z-score, lower milk intake and longer duration of EBF. Our findings might indicate that overweight prior to pregnancy can affect breastfeeding and thereby possibly the infant.