Low levels of PAPP-A and perinatal complications

In frozen-thawed embryo transfer (FET), differences in endometrial preparation methods affect the incidence of perinatal complications. However, the underlying causes are unclear. We aimed to investigate whether serum E2, P4 levels are associated with perinatal complications. This is a retrospective cohort study, involving 306 successful FET pregnancies from 2017 to 2022. Participants were divided into Natural Cycle (NC) and Hormone Replacement Cycle (HRC) group. We compared serum hormone levels, maternal backgrounds, and perinatal outcomes and complications. Furthermore, within the HRC group, serum hormone levels were compared for perinatal complications previously reported to show differences in incidence rates depending on the method of endometrial preparation. HRC exhibited significantly higher serum E2 levels during the implantation period, but lower P4 levels during ovulation, implantation, and pregnancy test period compared with NC. HRC also had significantly higher rates of postpartum hemorrhage (PPH) and placenta accreta spectrum (PAS). There was no association found between perinatal complications more likely to occur in HRC and serum E2, P4 levels. In HRC, there were more occurrences of PPH and PAS. Although serum E2, P4 levels during FET did not correlate with perinatal complications.

Replicated evidence indicates that perinatal complications are associated with increased markers of oxidative stress and with mental health problems in children. However, there are fewer reports on the impact of perinatal complications in later phases of development. We aimed to investigate the estimated effects of perinatal complications on levels of lipid peroxidation and on psychopathology in children and adolescents. The study is part of the High Risk Cohort Study for Psychiatric Disorders; the population was composed by 554 students, 6-14years of age. Serum levels of malondialdehyde, a product of lipid peroxidation, were measured by the TBARS method. A household interview with parents and caregivers was conducted and included inquiries about perinatal history, the Child Behavior Checklist (CBCL), and parent's evaluation, using the Mini International Psychiatric Interview (MINI). We created a cumulative risk index, conceptualized as each individual's cumulative exposure to perinatal complications. Results indicate that perinatal complications were associated with higher levels of TBARS. After adjusting for age, gender, socio-economic status, CBCL total problems score, parental psychopathology, and childhood maltreatment, children exposed to 3 or more perinatal complications had an 26.9% (95% CI 9.9%, 46.6%) increase in TBARS levels, relative to the unexposed group. Exploratory mediation analysis indicated that TBARS levels partially mediated the association between perinatal complications and externalizing problems. In conclusion, an adverse intrauterine and/or early life environment, as proxied by the cumulative exposure to perinatal complications, was independently associated with higher levels of lipid peroxidation in children and adolescents.

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies’ quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM.

Background/ObjectivesPregnancy complications are associated with adverse maternal–neonatal outcomes, but the underlying immune mechanisms remain unclear. Here we examined umbilical cord IL-17A levels and their link to gestational diabetes mellitus (GDM) and perinatal infections (PIs).MethodsThis two-phase study analyzed 87 pregnant women (38 in the exploratory phase and 49 in the validation phase) from Shenzhen's Premature Infants Gut Microbiota Assembly and Neurodevelopment (PIGMAN) cohort, divided into perinatal complication (PC) (45 cases) and non-perinatal complication (NPC) (42 cases) groups. Cord blood IL-17A levels were measured by ELISA and analyzed as a continuous variable by Nonparametric rank-sum test and a categorical variable using Fisher's exact test.ResultsNonparametric analysis revealed consistently lower IL-17A levels in the PC group across both phases. The discovery phase median in the PC group was 0.67 pg/ml lower than the 5.68 pg/ml median in the NPC group (p = 0.001); in the validation phase, the PC and NPC group levels were 0.93 and 2.05 pg/ml (p = 0.012), respectively. Low IL-17A (<1 pg/ml) prevalence was significantly higher in PC cases (discovery: 61.9% vs. 11.8%, p = 0.002; validation: 50% vs. 36%, p = 0.031). Rank-sum test and Fisher's exact test demonstrated concordant results, confirming a robust association between reduced IL-17A levels and perinatal complications.ConclusionUmbilical cord blood from PC pregnancies exhibited significantly lower IL-17A levels compared to that from NPC pregnancies, suggesting compromised neonatal cellular immunity. These findings implicate IL-17A deficiency in the immune dysregulation associated with GDM and PI. Conversely, the higher IL-17A levels observed in NPC pregnancies may reflect its protective role in maternal–fetal immunity during early development.

We have investigated cord blood granulocyte-colony stimulating factor (G-CSF) levels in neonates with or without neonatal complications to examine some changes in the G-CSF levels in the neonatal period. The G-CSF levels were measured in 613 neonates by enzyme immunoassay. The results showed that G-CSF levels were distributed in a broad range from the level under the cutting point (31 pg/mL) to over the measurable range (2000 pg/mL). Normal neonates without perinatal complications were 322. In normal neonates, the G-CSF level correlated with the gestational age (r = 0.255, P < 0.01) and cord blood leukocyte count (r = 0.210, P < 0.01). The G-CSF values were under 100 pg/mL in 95% of normal neonates with a median of 35.0 pg/mL. We divided the neonates into two groups: a lower (< 100 pg/mL) and a higher (> or = 100 pg/mL), based on the G-CSF level. The percentage of neonates with higher G-CSF levels (> or = 100 pg/mL) was greater in neonates with perinatal complications than in normal neonates (< 100 pg/mL; P < 0.01). Compared with normal neonates, the percentages of the higher group were greater in neonates with infections (P < 0.01), fetal distress (P < 0.01), premature rupture of membranes (P < 0.05), neonatal asphyxia (P < 0.01) and meconium staining of amniotic fluid (P < 0.01). Neonates with higher G-CSF levels had larger numbers of peripheral leukocytes (P < 0.05) than did those with the lower G-CSF levels. Counts of leukocytes were parallel with those of neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

BackgroundCommon pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age.MethodsWe used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1–1.6 years), childhood (4.2–7.5 years); adolescence (12.0–16.0 years), and adulthood (22.0–67.8 years).ResultsOffspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of −0.89 standard deviation (SD) units for albumin with PTB (95% CI: −1.10 to −0.69, P=1.3×10−17) and −0.41 SD for total lipids in medium HDL with SGA (95% CI: −0.56 to −0.25, P=2.6×10−7), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. −0.11 SD total fatty acids, 95% CI: −0.18 to −0.05, P=0.0009), and attenuating with older age across adulthood.ConclusionsThese reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.

Influence of thyroid peroxidase antibodies on TSH levels of pregnant women and maternal–fetal complications

Influencia de los anticuerpos antiperoxidasa tiroidea en los valores de TSH de gestantes y en las complicaciones materno-fetales

Increased macrophage-colony stimulating factor levels in neonates with perinatal complications.

Association of serum interleukin-6 with mental health problems in children exposed to perinatal complications and social disadvantage

ObjectiveTo investigate clinical factors affecting the timing of delivery in twin pregnancies in order to minimize perinatal complications.MethodsA retrospective study involved 163 twin pregnancies delivered from January 2006 to September 2011 at Gachon University Gil Medical Center. These cases were divided into three groups based on the delivery timing: less than 32 weeks' gestation (group A), between 32 and 35+6 weeks' gestation (group B), and over 36 weeks' gestation (group C). Clinical factors including maternal age, parity, presence of premature uterine contraction, presence of premature rupture of membrane, white blood cell, high sensitive C-reactive protein level, cervical dilatation, maternal complication, chorionicity, twin specific complication, and perinatal complication were analyzed for each group.ResultsIn group B, the timing of delivery was postponed for 14 days or more from the time of admission, and there were fewer numbers of babies with low Apgar score at birth compared with other groups. The frequency of uterine contraction (P<0.001), presence of premature rupture of membranes (P=0.017), dilatation of cervix (P<0.001), increased white blood cell and high sensitive C-reactive protein levels (P=0.002, P<0.001) were important clinical factors during decision making process of delivery timing in twin pregnancies. Twin specific fetal conditions, such as twin-twin transfusion syndrome and discordant growth (over 25% or more) were shown more frequently in group A. However, there were no significant statistical differences among three groups (P=0.06, P=0.14).ConclusionProper management for preventing premature contraction and inflammation can be essential in twin pregnancies until 32 weeks' gestation, and may decrease maternal and perinatal complications.

Background. Intrahepatic cholestasis of pregnancy (COP) is the most common complication of pregnancy that occurs during the 2nd-3rd trimester and is accompanied by liver damage manifested as cholestasis and cytolysis. Objective. To establish the role of cytokine response in the pathogenesis of COP as well as its obstetric and perinatal complications. Material and methods. 87 pregnant women were examined: 57 with intrahepatic cholestasis of pregnancy and 30 patients of the comparison group. The levels of pro-inflammatory (interleukin 6) and anti-inflammatory (interleukin 4) cytokines were determined by enzyme-linked immunosorbent assay, and their prognostic significance as predictors of obstetric and perinatal complications in women with COP was estimated. Results. The course of COP is accompanied by a decrease in the concentrations of IL-6 and IL-4 cytokines and a lower ratio of IL-4/IL-6 (P(U)IL-6=0.041; P(U)IL-4=0.0007 and P(U)IL4/IL-6=0.008). The concentration of IL-6 in blood serum that is &gt; 2.53 pg/ml (Se=83.3 %, Sp=73.9 %; AUC=0.822; 95 % CI 0.636–0.938; p=0.004) and IL-4 concentration that is &gt; 41.99 pg/ml in symptomatic COP (Se=100.0 %, Sp=78.6 %; AUC=0.839; 95 % CI 0.593–0.965; p=0.011) are regarded as a risk factor for preterm labor (PL) in women with COP. The concentration of IL-6 &gt; 3.07 pg/ml in women with COP and negative vaginal discharge culture can be considered as a predictor of meconium staining of amniotic fluid (MSAF) (Se=100.0 %, Sp=62.9 %; AUC=0.770; 95 % CI 0.597–0.895; p=0.024). Conclusions. COP is accompanied by a lower level of IL-6; an atypical immune deviation with no shift towards the Th2 immune response that is characteristic of a normal pregnancy; as well as an imbalance in the cytokine response with a decrease in the anti-inflammatory link. Preterm birth in patients with COP is associated with higher levels of IL-6 during pregnancy. The release of meconium into amniotic fluid in women with COP (in the absence of significant pathogenic and opportunistic microflora according to the results of vaginal discharge culture) correlates with higher concentrations of IL-6 in the blood.

Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28–32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23–0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24–5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

We tested the effect of patient compliance, fasting plasma glucose on oral glucose tolerance test, maternal body constitution, and the method of treatment (diet versus insulin) on the perinatal outcome of patients with gestational diabetes mellitus. A prospective population-based study compared the perinatal outcome of patients with gestational diabetes mellitus (n = 470) (diabetic with regard to the parameters specified above) and a contemporaneous control group (nondiabetic, n = 250). The diabetic and control groups were matched in demographic characteristics. Patient compliance reduced the rate of macrosomia (14.4%) and neonatal hypoglycemia (3.4%) but not to the levels of the control group (5.2% and 1.2% respectively, p < 0.05). The level of fasting plasma glucose on the oral glucose tolerance test had no effect on perinatal outcome. Intensified (insulin) treatment reduced the rate of macrosomia and large-for-gestational age infants in the subgroups with intermediate and high levels of fasting plasma glucose on the oral glucose tolerance test (9.5%/14.2% and 12.2%/24.2% respectively), again not to levels of the control group (5.2%/10.8%). Obese patients were found to have more perinatal complications than lean patients. Intensified (insulin) treatment has proved to be beneficial in terms of reducing the rate of perinatal complications in the obese patients, but not to the corresponding levels of the control group. Such treatment had no effect on the lean patients. Strict control of maternal hyperglycemia and high patient compliance are imperative for an effective reduction of perinatal complication in patients with gestational diabetes mellitus. The desired plasma glucose level in the glycemic control of these patients should be further reduced, thus bringing the rate of perinatal complications to that of the normal population.

The objective: to reduce the frequency of obstetrical and perinatal complications in women of late reproductive age, whose pregnancy occurred with the help of assisted reproductive technologies (ART).Materials and methods. 150 nulliparous women of late reproductive age with a singleton pregnancy and fetal head presentation without severe somatic and gynecological pathology and fetal malformations, were examined. All patients were randomly divided into three groups: the main group (50 pregnant women after the ART program (n1), who received the developed algorithm – diagnosis, prevention and therapy of gestational anemia, diagnosis and prevention of intranatal complications, prevention of prolonged pregnancy, prevention of hemorrhagic complications, screening, prevention and therapy of perinatal psychological disorders; comparison group (50 patients with ART pregnancy, n2), and control group (50 patients with spontaneous pregnancy, n3). Pregnancy, childbirth and the postpartum period in the patients of the comparison group and the control group were conducted in accordance with the orders of the Ministry of Health of Ukraine. All women had a complete clinical and laboratory examination during pregnancy, childbirth and in the postpartum period, as well as a study of the level of anxiety, sleep quality, and assessment of the development of postpartum depression. Results. During the pregnancy course the percentage of patients with gestational anemia significantly decreased in the main group and was 2.0% versus 30.0% in the comparison group and 18.0% in the control group (р1.2;р1.3&lt;0.05). In the postpartum period, the rate of anemia was also significantly lower in the main group than in the comparison and control groups.26% of patients in the comparison group and 14% – in the control group had labor induction in the term of 40–41 weeks, in the same gestational term 20% of patients in the main group were delivered by the plan caesarean section because of the absence of spontaneous onset of regular labor activity. There was no significant difference in the frequency of normal delivery and cesarean section between the main and comparison groups, but the extensive frequency of urgent cesarean section was significantly lower in the main group and it was 52% versus 83.3% in the comparison group and 86.7% – in the control group (р1.2;р1.3&lt;0.05). The mean volume of blood loss in the main group was significantly less than in the comparison group – 300.0 (250.0; 642.5) ml versus 690.0 (300.0; 800.0) ml (р1.2&lt;0.001) and did not significantly differ from this indicator in the control group - 300.0 (250.0; 600.0) ml. Mean volumes of blood loss separately during vaginal delivery and caesarean section in the main group were also significantly lower than in the comparison group, and were 250.0 (200.0; 280.0) ml versus 300.0 (255.0; 350.0) ml (р1.2=0.004) and 650.0 (610.0; 740.0) ml versus 750.0 (700.0; 800.0) ml (р1.2=0.01), respectively . As pregnancy progressed, the patients in the comparison and control groups were more prone to high anxiety and sleep disturbances. For the patients of the comparison group, in contrast to the women of the main group, there was a significant increase in the time required to fall asleep, the frequency of awakenings during the night, women more often needed to use sleeping pills and complained of excessive sleepiness during the day and, accordingly, had significantly lower indicators of subjective evaluation sleep quality. At 35–37 weeks of pregnancy, the rate of patients with high levels of state and trait anxiety was significantly lower in the main group than in the comparison group (28.0% vs. 66.0% and 14.0% vs. 52.0% , respectively; p1,2&lt;0.05). Immediately after delivery, levels of both state and trait anxiety decreased slightly in all study groups, but the validity of the differences remained constant. The frequency of patients with a moderate risk of the postnatal depression development was 16% in the main group, 36% – in the comparison group (p1.2&lt;0.05) and 20% – the control one. In 6-8 weeks after childbirth, on the background of gaining the necessary experience, there is a moderate improvement in the quality of sleep and a significant decrease in anxiety levels in all groups. The rate of patients with a moderate risk of depression development in this term remained lower in the main group than in the comparison group (12% vs. 38% ; p1.2&lt;0.05), in the control group this indicator was 18% . Conclusions. The study proved the feasibility, efficacy, and safety of the treatment and diagnostic algorithm for prevention the obstetrical and perinatal complications in patients in late reproductive age who became pregnant after the use of ART.