Maternal and Neonatal Factors Modulating Breast Milk Cytokines in the First Month of Lactation.

Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (ß = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (ß = -0.64 ± 0.27, p = 0.019; ß = -0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processes.

Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features.

BACKGROUND: Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome. OBJECTIVE: To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia. STUDY DESIGN: This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34 week's gestation) severe preeclampsia. RESULTS: 63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]). CONCLUSIONS: The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.

Continuous glucose monitoring in individuals undergoing gestational diabetes screening.

BACKGROUND: Among guidelines on gestational diabetes mellitus, there is an incongruity about the threshold of maternal hyperglycemia to diagnose gestational diabetes mellitus. OBJECTIVE: This study aimed to ascertain the association between continuous glucose monitoring metrics and adverse outcomes among individuals undergoing gestational diabetes mellitus screening. STUDY DESIGN: This was a prospective study (from June 2020 to January 2022) of individuals who underwent 2-step gestational diabetes mellitus screening at ≤30 weeks of gestation. The participants wore a blinded continuous glucose monitoring device (Dexcom G6 Pro; Dexcom, Inc, San Diego, CA) for 10 days starting when they took the 50-g glucose challenge test. The primary outcome was a composite of adverse neonatal outcomes (large for gestational age, shoulder dystocia or neonatal injury, respiratory distress, need for intravenous glucose treatment for hypoglycemia, or fetal or neonatal death). The secondary neonatal outcomes included preterm birth, neonatal intensive care unit admission, hypoglycemia, mechanical ventilation or continuous positive airway pressure, hyperbilirubinemia, and hospital length of stay. The secondary maternal outcomes included weight gain during pregnancy, hypertensive disorders of pregnancy, induction of labor, cesarean delivery, and postpartum complications. Time within the target range (63-140 mg/dL), time above the target range (>140 mg/dL) expressed as a percentage of all continuous glucose monitoring readings, and mean glucose level were analyzed. The Youden index was used to choose the threshold of ≥10% for the time above the target range and association with adverse outcomes. RESULTS: Of 136 participants recruited, data were available from 92 individuals (67.6%). The 2-step method diagnosed gestational diabetes mellitus in 2 individuals (2.2%). Continuous glucose monitoring indicated that 17 individuals (18.5%) had time above the target range of ≥10%. Individuals with time above the target range of ≥10% had a significantly higher likelihood of composite adverse neonatal outcomes than individuals with time above the target range of <10% (63% vs 18%; P=.001). Furthermore, compared with neonates born to individuals with time above the target range of <10%, neonates born to individuals with time above the target range of ≥10% had an increased likelihood for hypoglycemia (14.5% vs 47%; P=.009) and had a longer length of stay (2 vs 4 days; P=.03). No difference in maternal outcomes was noted between the groups. CONCLUSION: In this prospective study of individuals undergoing gestational diabetes mellitus screening, a cutoff of the time above the target range of ≥10% using continuous glucose monitoring was associated with a higher rate of neonatal adverse outcomes. A randomized trial of continuous glucose monitoring vs 2-step screening for gestational diabetes mellitus to lower the rate of adverse outcomes is underway (identification number: NCT05430204).

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with vitamin B12 deficiency and adverse perinatal outcomes among pregnant women of rural South India - a cross sectional longitudinal study.

OBJECTIVES: To determine the occurrence of MTHFR gene polymorphisms and to study their association with vitamin B12 deficiency and adverse perinatal outcomes among a cohort of pregnant women from Kaniyambadi block, Tamil Nadu. METHODS: 120 consecutive pregnant women who were ≤20 weeks of gestational age from the 82 villages of Kaniyambadi block were recruited. Genomic DNA was isolated from the peripheral blood. PCR amplification was done followed by Sangers sequencing. Maternal and neonatal outcomes were extracted. Data was entered and analysed. RESULTS: Our study found the occurrence of c.1298A>C variant in homozygous state in 14.2% and c.677C>T heterozygous state in 15%. Sanger sequencing of exon 7 identified another pathogenic variant c.1262G>T in heterozygous state in two of them. Both the mothers who harboured that variant had preterm delivery and one of them gave birth to a low-birth-weight neonate. In the entire cohort, 5% of the mothers had abortion, 4.2% of them had preterm delivery and 8.8% of the neonates had low birth weight. Presence of c.1298A>C or c.677C>T variants were associated with vitamin B12 deficiency [Pearson Chi squared value (χ2)=7.9 and 7.6 respectively; p=0.02]. Heterozygous pathogenic variant c.1262G>T was associated with both adverse maternal [χ2=11.5; p=0.001] and neonatal [χ2=18.3; p=0.009] outcomes. CONCLUSIONS: MTHFR gene polymorphisms could be associated with several adverse perinatal outcomes and vitamin B12 deficiency. Further larger studies are needed to prove the pathogenicity of c.1262G>T variant on pregnancy.

Association between apgar score at 5 minutes and adverse outcomes among Low-Risk pregnancies.

OBJECTIVE: Among low-risk pregnancies, we aimed to ascertain the association between 5-minute Apgar score and adverse outcomes of newborn-maternal dyad. STUDY DESIGN: We conducted a retrospective cohort study using the U.S. vital statistics datasets (2012-2016), including live births from low-risk women with non-anomalous singleton gestations who delivered at 37-41 weeks. Apgar score was categorized as low (0-3), moderate (4-6), and normal (7-10). The primary outcome was composite neonatal adverse outcome (any of the following: assisted ventilation > 6 h, neonatal seizure, or neonatal death). The secondary outcomes were infant mortality and composite maternal adverse outcome (any of the following: admission to the intensive care unit, blood transfusion, uterine rupture, or unplanned hysterectomy). Multivariable Poisson regression analyses were used to estimate the association between 5-minute Apgar score and adverse outcomes (using adjusted relative risk [aRR] and 95% confidence intervals [CI]). RESULTS: Of 19.9 million live births delivered between 2012 and 2016, 11.7 million (58.7%) met inclusion criteria; 98.9% had a normal 5-minute Apgar score, 0.9% had a moderate score, and 0.2% had a low score. The overall composite neonatal adverse outcome was 3.2 per 1,000 live births and the rates were significantly higher among those with a moderate (aRR 20.8; 95% CI 20.2-21.4) or low score (aRR 43.1; 95% CI 41.6-44.5) than normal score. The overall composite maternal adverse outcome was 2.45 per 1,000 live births and it was significantly higher in deliveries with a moderate (aRR 3.1; 95% CI 2.9-3.3) and low (aRR 4.6; 95% CI 4.2-5.0) 5-minute Apgar score than those with a normal score. Infant mortality also showed a similar pattern. CONCLUSION: Though approximate 1% of live births had a 5-minute Apgar score below 7 among low-risk pregnancies, a decreased score was associated with a significantly higher risk of neonatal and maternal adverse outcomes, as well as infant mortality.

Apgar score at 10 minutes and adverse outcomes among low-risk pregnancies.

OBJECTIVE: Among low-risk pregnancies, we ascertained the association between 10-minute Apgar score and adverse outcomes of newborn infants. METHOD: We conducted a retrospective cohort study using the U.S. vital statistics datasets (2011-2018), which included live births from low-risk women with non-anomalous singleton gestations who delivered at 37-41 weeks. When a newborn infant had an abnormal 5-minute Apgar score (0-5), a 10-minute Apgar score was documented in the birth certificate. Apgar score at 10 min was categorized as low (0-3), moderate (4-6), and normal (7-10). The primary outcome was composite neonatal adverse outcome. The secondary outcomes were individual neonatal adverse outcomes and infant mortality. Multivariable Poisson regression analyses were used to estimate the association between 10-minute Apgar score and adverse outcomes (using adjusted relative risk [aRR] and 95% confidence intervals [CI]). RESULTS: Of 31.5 million live births delivered (2011-2018), 111,163 (0.4%) met inclusion criteria; of them, 74.2%, 20.7%, and 5.1% had normal, moderate, and low 10-minute Apgar scores, respectively. The overall composite neonatal adverse outcome was 100.6 per 1,000 live births and the risk was significantly higher among those with a moderate (aRR 3.19; 95% CI 3.06-3.31) or low 10-minute Apgar score (aRR 6.62; 95% CI 6.34-6.91) than with a normal 10-minute Apgar score. Infant mortality also showed a similar pattern. Newborn infants with improved Apgar scores from 5 to 10 min were associated with lower risks of the composite neonatal adverse outcome, as well as infant mortality, than those with scores that remained stable. CONCLUSION: Among low-risk pregnancies, newborn infants with a lower 10-minute Apgar score were associated with a higher risk of adverse outcomes.

Correlations between the proportion of type III female genital mutilations in the series and adverse obstetric outcomes: a short meta-analysis.

Background: Authors have reported that evidence on health harms of female genital mutilation is poor.Aim: Meta-analyzing prospective studies on adverse obstetric outcomes according to the severity of female genital mutilation.Method: Prospective studies were already acknowledged in previous meta-analyses and used for calculations. The proportions of type III female genital mutilation were extracted by full-texts, along with the proportions of adverse obstetric outcomes. Assuming random models, the proportions were encoded for meta-analysis and weighted for the inverse of the variance. Nonparametric correlations among weighted proportions of type III female genital mutilation and weighted proportions of obstetric outcomes were built. Analyzable obstetric outcome were: cesarean section, instrumental delivery, episiotomy, post-partum hemorrhage, low Apgar score - need of resuscitation.Results: Meta-analyzable series are few and heterogeneous. There is a trend of direct correlation among the proportion of type III female genital mutilations in the series and the proportion of cesarean section, instrumental deliveries, post-partum hemorrhage and low Apgar scores at birth or need of neonatal resuscitation. The significance was reached for the post-partum hemorrhage and for the fetal adverse outcome.Conclusion: It should be retained that type III female genital mutilation is likely to be a serious concern for birth.

The impact of placental massive perivillous fibrin deposition on neonatal outcome in pregnancies complicated by fetal growth restriction.

INTRODUCTION: Massive perivillous fibrin deposition (MPDD) is an uncommon placental lesion which has been associated with an increased risk of adverse pregnancy outcome in retrospective series. The purpose of the study was to evaluate the frequency and consequences of MPFD in pregnancies complicated by fetal growth restriction (FGR). MATERIALS AND METHODS: A cohort study of 355 pregnancies complicated by FGR diagnosed according to standard ultrasonographic criteria, enrolled, followed and delivered at a single obstetric unit. Pathological placental lesions were classified according to the Amsterdam Placental Workshop Consensus. Penalized logistic regression models were used to evaluate the association of MPFD with maternal risk factors, other pathological lesions and neonatal outcome. RESULTS: The rates of moderate (25-50% of villi) and severe (>50% of villi) MPFD were 8.7% (31/355) and 3.1% (11/355), respectively. Compared to other FGR cases, MPFD pregnancies were characterized by higher placental volume (450 ±â€¯144.5 SD as compared to 412.2 ±â€¯151 cm3,p < 0.001) and lower birthweight/placental weight ratio (5.32 ±â€¯1.53 compared to 6.1 ±â€¯1.52,p < 0.001). The rates of abnormal Doppler ultrasound studies of umbilical and middle cerebral artery were similar in MPFD subjects and controls. After correction for gestational age and birthweight, MPFD was associated with an increased risk of neonatal intraventricular hemorrhage (>grade II) (OR = 5.66,95% CI = 1.69-18.97), sepsis (OR = 5.9, 95% CI = 1.27-27.12), proven necrotizing enterocolitis (OR = 9.84,95% CI = 2.49-38.8) and overall severe adverse neonatal outcome (OR = 5.71,95% CI = 2.05-15.87). CONCLUSIONS: Moderate-to-severe MPFD was relatively common among FGR pregnancies and was associated with morphometric modifications of placenta and with an increased risk of severe adverse neonatal outcome.