Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

PURPOSE: Overt hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications. METHODS: Group 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10 mU/L, > 10 µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5-2.5 mU/L, 0.5-2.5 µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale. RESULTS: Pregnancy outcome showed an average gestational age at delivery of 38.2 weeks for hypothyroid women, compared to 40 weeks for controls, and average birth weight of 2855.6 g versus 3285 g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores. CONCLUSION: Fetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Mode of delivery and peripartum outcome in women with heart disease according to the ESC guidelines: an Italian multicenter study.

INTRODUCTION: The European Society of Cardiology (ESC) guidelines (GL) provide indications on the mode of delivery in women with heart disease. However available data suggests that the rate of Cesarean Delivery (CD) is high and widely variable among such patients. In this study, we aimed to investigate the degree of adherence to the ESC recommendations among women delivering in four tertiary maternity services in Italy and how this affects the maternal and neonatal outcomes. MATERIAL AND METHODS: Retrospective multicenter cohort study including pregnant women with heart disease who gave birth between January 2014 and July 2020. Composite adverse maternal outcome (CAM) was defined by the occurrence of one or more of the following: major postpartum hemorrhage, thrombo-embolic or ischemic event, de novo arrhythmia, heart failure, endocarditis, aortic dissection, need for re-surgery, sepsis, maternal death. Composite Adverse Neonatal outcome (CAN) was defined as cord arterial pH <7.00, APGAR <7 at 5 min, admission to the intensive care unit, and neonatal death. We compared the incidence of CAM and CAN between the cases with planned delivery in accordance (group "ESC consistent") or in disagreement (group "ESC not consistent") with the ESC GL. RESULTS: Overall, 175 women and 181 liveborn were included. A higher frequency of CAN was found when delivery was not planned accordingly to the ESC guidelines [("ESC consistent" 9/124 (7.2%) vs "ESC not consistent" 13/57 (22.8%) p = 0.002 OR 3.74 (CI 95% 1.49-9.74) , while the occurrence of CAM was comparable between the two groups. At logistic regression analysis, the gestational age at delivery was the only parameter independently associated with the occurrence of CAN (p = 0.006). CONCLUSION: Among pregnant women with heart disease, deviating from the ESC guidelines scheduling cesarean delivery does not seem to improve maternal outcomes and it is associated with worse perinatal outcomes, mainly due to lower gestational age at birth.

Complementemia in pregnancies with antiphospholipid syndrome.

Prognosis of pregnancies in women with antiphospholipid syndrome has dramatically improved over the past two decades using conventional treatment with low molecular weight heparin and low-dose aspirin. However, despite this regimen, 10-15% of antiphospholipid syndrome patients experience pregnancy losses. Several studies have been performed in order to identify risk factors predictive of complications. Thrombosis has been generally accepted as the key pathogenetic mechanism underlying pregnancy morbidity. However, the thrombogenic state alone is not able to explain all the different mechanisms leading to pregnancy failure. In fact, emerging evidence shows that complement pathway could play an important role in mediating clinical events in antiphospholipid syndrome. However, the exact mechanism through which complement mediates antiphospholipid syndrome complications remains unknown. Low complement levels (C3 and C4) are associated with poor pregnancy outcome in women with antiphospholipid syndrome in different studies. Hypocomplementemia could be indicated as an early predictor of adverse pregnancy outcome, available at the beginning of pregnancy for starting, if necessary, additional treatment to conventional therapy. However, future studies need to better understand the impact of low complement level on antiphospholipid syndrome pregnancy outcome.

Gestational weight gain as an independent risk factor for adverse pregnancy outcomes in women with gestational diabetes.

OBJECTIVE: Obesity and gestational diabetes mellitus (GDM) are rising worldwide. This study retrospectively evaluated the role of excessive gestational weight gain (eGWG) in women with GDM and different pre-pregnancy body mass indices (BMIs). PATIENTS AND METHODS: Optimal glycaemic control was defined as achieving glucose target thresholds in more than 80% of measurements. 283 women with GDM were categorized as underweight, normal weight, overweight or obese based on WHO's classification scheme. eGWG was defined as >18.0 kilograms for women who were underweight, >15.8 kilograms for those who were normal weight, >11.3 kilograms for those who were overweight and >9.0 kilograms for those who were obese. For the analysis, women were divided into two groups: normal and excessive GWG. The main outcomes measured were incidences of large/small for gestational age (LGA/SGA), macrosomia, preterm delivery, hypertensive disorders and caesarean sections (CS). RESULTS: Excessive GWG was associated with higher birth weight and percentile (p<0.001), and with a higher prevalence of LGA (p<0.001), macrosomia (p=0.002) and hypertensive disorders (p=0.036). No statistical differences were found for the week of delivery, or prevalence of CS and SGA. The multivariate analysis highlighted both pre-pregnant BMI and eGWG as independent risk factors for LGA and macrosomia. Women with a pre-pregnant BMI of at least 25 and eGWG have a 5.43-fold greater risk of developing LGA (p=0.005). CONCLUSIONS: When combined with an inadequate pre-pregnant BMI, eGWG acts as a "synergic risk factor" for a poor outcome. When obesity or GDM occur, an optimal GWG can guarantee a better pregnancy outcome.

Influence of Biliopancreatic Diversion on Pregnancy Outcomes in Comparison to Other Bariatric Surgery Procedures.

BACKGROUND: Pregnancy after bariatric surgery (BS) has an increased risk for small-for-gestational-age infants (SGA), shorter length of gestation, and probably perinatal mortality. The aim of this study was to investigate if biliopancreatic diversion could impair pregnancy outcomes in comparison to other bariatric surgery procedures. METHODS: We conducted a cohort retrospective single-center study in 65 women before and after BS. Thirty-one pregnancies occurred before BS, while 109 after BS, amongst which n = 51 after biliopancreatic diversion (BPD) and n = 58 after non-malabsorptive procedures. RESULTS: The pregnancy outcomes after BS in comparison with those before BS resulted less affected by diabetes, hypertensive disorders, macrosomia, and large-for-gestational-age (LGA), but more complicated by preterm births (14.5 versus 4.0%) and low birth weight (LBW) infants (28.9 versus 0%). Moreover, mean birth weight resulted lower after BS than before BS (p < 0.001). In pregnancies after BPD in comparison to those before BS, the LBW rate (42.5%) resulted a drastic increase (p < 0.001), and mean birth weight (p < 0.001) and mean birth weight centile (p < 0.001) were lower after BPD. When pregnancy outcomes after BPD were compared with those after non-malabsorptive procedures, the rate of congenital anomalies, preterm births, LBW, and SGA resulted an increase (p = 0.002, 0.008, 0.032, and < 0.001, respectively). CONCLUSIONS: BPD drastically reduced diabetes, hypertensive disorders, macrosomia, and LGA; however, it was associated with the poorest pregnancy outcomes in comparison to those observed after other BS procedures. On the basis of the present study, we recommend a cautious multidisciplinary selection of severely obese patients for BPD during the fertile age.

Association between false-positive TORCH and antiphospholipid antibodies in healthy pregnant women.

The present study investigated: (a) the presence of antiphospholipid antibodies and (b) the obstetric outcome in healthy pregnant women showing false-positive TORCH-Toxoplasmosis, Other: syphilis, varicella-zoster, Rubella, Cytomegalovirus (CMV), and Herpes infections-results. Data from 23 singleton healthy pregnancies with false-positive TORCH results were collected. Each woman was systematically screened for TORCH IgG and IgM during the pre-conception assessment and/or at the beginning of pregnancy. In the presence of IgM positivity, when indicated (CMV, toxoplasmosis, rubella, herpes simplex virus), IgG avidity was evaluated and, if possible, polymerase chain reaction was performed on an amniotic fluid sample in order to distinguish between primary infection or false positivity. The antiphospholipid antibodies tests were: lupus anticoagulant, anticardiolipin antibodies IgG, IgM, and anti-ß2glicoprotein I IgG, IgM. The antiphospholipid antibodies tests, if positive, were repeated after 12 weeks to confirm the results. In pregnant women with false-positive TORCH, the overall prevalence of positive antiphospholipid antibodies for one or more tests was 52.2%. To clarify the correlation of false-positive TORCH results with clinical practice, obstetric outcome was analyzed in terms of live births, week of delivery, neonatal birth weight, and neonatal birth weight percentile. A statistically significant lower neonatal birth weight and neonatal birth weight percentile were observed in women with false-positive TORCH associated with antiphospholipid antibodies positivity (Group A) in comparison with those in women with false-positive TORCH without antiphospholipid antibodies positivity (Group B). No statistically significant difference was found for the week of delivery between the two groups. It is hoped that future studies will verify the life-long persistence of antiphospholipid antibodies positivity by follow-up of these women and identify who will develop a classical antiphospholipid syndrome or other autoimmune disorders.

Perinatal outcome in pregnant women with cancer: are there any effects of chemotherapy?

Cancer is the leading cause of death in women of reproductive age. During the last decades and especially in developed countries, the incidence of cancer is increasing dramatically, with an incidence of 1 in 1,000 pregnancies. This is mostly related to delay of pregnancy into the late reproductive years. The aim of this study was to investigate the outcome of pregnancy in women with diagnosis of cancer; in particular, neonatal morbidity and mortality, after in utero exposure to chemotherapy, were evaluated. A total of 59 singletons and one twin pregnancy complicated by cancer were followed at our tertiary centre over the last 15 years. A different treatment, based on surgery and/or chemotherapy in pregnancy or delayed to the postpartum period, was employed. There were 59 live births (97%), one foetal loss and one stillbirth at 28 weeks. The congenital malformation rate was 5% (n = 3). The rate of preterm birth was 83%. The mean birthweight and mean birthweight percentile were 2,098 g (740-3930) and 46 (7-93), respectively; 32% of neonates were small for gestational age (SGA). Dividing the population into treated or untreated with chemotherapy, the rate of SGA was not statistically significant different between the two groups. Our results showed that chemotherapy administered during the second trimester or later did not influence intrauterine foetal growth, but the high prevalence of SGA neonates in the two groups, exposed or not exposed to chemotherapy, suggests an influence of maternal cancer per se on foetal growth.

The transition from intra to extra-uterine life in late preterm infant: a single-center study.

BACKGROUND: Infants born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse outcomes than those born at 37 weeks of gestation or later. Aim of this paper is to examine risk factors for late preterm births and to investigate the complications of the transition period in late preterm infants (LPIs). METHODS: All consecutive late preterm deliveries, excluded stillbirths, were included. Maternal and neonatal data, need for delivery room resuscitative procedures, temperature at birth (T1) and two hours after the admission (T2) were analyzed in all LPIs stratified by Gestational Age (GA) and divided into three groups (34, 35 and 36 weeks). RESULTS: Two hundred seventy-six LPIs were analyzed. Pregnancy complications were present in 72 mothers (26.1 %), more frequently at 34 weeks of gestation respect to 35 and 36 weeks (p = 0.008, p = 0.006 respectively). Forty seven LPIs (17.1 %) needed for any resuscitation and 37 (13.4 %) were ventilated at birth. LPIs at 34 weeks were significantly more likely to receive ventilation respect to those at 35 and 36. At T1 the mean temperature resulted lower at 34 weeks respect to 36 weeks (p = 0.03). At T2 respect to T1, the rate of normothermic neonates increased at 35 and 36 weeks (p = 0.003, p = 0.005, respectively). Hypoglicemia rate was similar among the groups; 66.7 % of hypoglicemic neonates were hypothermic at T1. The rate of respiratory diseases and NICU admission decreased with increasing GA. Higher number of neonates ventilated at birth developed respiratory disorders respect to those unventilated (40.5 % vs 8.4 %; p < 0.001). CONCLUSIONS: Transition period in LPIs may become critical, as resuscitation strategies can be required and heat loss can occur. LPIs, especially at 34 gestational weeks, are higher-risk group needing adequate and targeted management at birth.

Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment?

The best therapy regimen for refractory obstetrical antiphospholipid syndrome remains to be determined. Additional treatments with steroids, plasma exchanges and immunoglobulins failed to show any beneficial effect. We present a case of a woman who had a better pregnancy outcome after the administration of hydroxychloroquine (HCQ) as additional treatment. Furthermore, we highlighted that HCQ was able to dramatically reduce the antiphospholipid antibodies levels.

Fondaparinux in pregnancy: Could it be a safe option? A review of the literature.

During pregnancy thrombo-prophylaxis could be required in high risk women. If a severe allergic reaction to low-molecular-weight-heparin (LMWH) or a heparin-induced-thrombocytopenia (HIT) occurs, it's mandatory to stop the drug. Fondaparinux could be an effective option. In the present review, the maternal and pregnancy outcomes of 65 pregnancies in women using Fondaparinux were reported. It was well-tolerated and rate of pregnancy complications was similar to that observed in general population. Regarding congenital malformations, further studies are necessary to investigate the safety of the drug.

Cerebral sinovenous thrombosis in neonatal antiphospholipid syndrome: a new entity?

Neonatal antiphospholipid syndrome (neonatal APS) seems to be exceedingly rare, as the antiphospholipid antibodies (aPL) related thrombosis in the neonatal period. The pathogenesis of perinatal aPL related thrombosis may be explained both by the transplacental passage of the maternal antibodies and by the production of de novo antibodies by the neonate. However, few cases of neonatal APS are reported in the literature, especially regarding arterial thrombotic events. In particular, only two cases of neonatal aPL related isolated cerebral sinovenous thrombosis (CSVT) are described in the literature. Despite its frequency, CSVT results in significant mortality and morbidity, probably also due to the difficulty in early diagnosis and then in correct managing in the neonatal period. A diagnosis of neonatal APS should be considered in the evaluation of neonates with CSVT, as well as in any case of neonatal thrombosis, to correctly manage the affected neonates and counsel the mother for future pregnancies.

A case of heparin allergy with good tolerability to fondaparinux during pregnancy

No disponible

Follow-up of babies born to mothers with antiphospholipid syndrome: preliminary data from the European neonatal registry.

In this review preliminary data on the follow-up of 141 babies born to mothers with antiphospholipid syndrome are reported. In spite of maternal treatment, the rate of both preterm delivery and low birth weight were 16 and 17%, respectively. At birth, no clinical evidence of perinatal thrombosis was observed. Placental transfer of antiphospholipid antibodies occurred in 20, 25 and 43% of cases for lupus anticoagulant, anticardiolipin and anti-ß2-glycoprotein I antibodies, respectively. At 24 months of follow-up, four children showed behaviour abnormalities suggesting the possible need for long-term neurological evaluation in this clinical setting.

The relationship between TORCH complex false positivity and obstetric outcome in patients with antiphospholipid syndrome.

OBJECTIVE: The presence of TORCH IgM positivity is not a specific indicator of primary infection; the assessment of IgG avidity index has been shown to be useful in identifying or excluding primary infection in pregnant women with no pre-gestational TORCH serology. TORCH is an acronym for Toxoplasmosis, Others (HBV, syphilis, Varicella-Zoster virus, Epstein Barr virus, Coxsackie virus and Parvovirus), Rubella, Cytomegalovirus (CMV) and Herpes Simplex. PATIENTS AND METHODS: Data from 54 pregnancies in women with antiphospholipid syndrome (APS) were assessed in comparison with data from 222 healthy pregnant women as controls. Each woman in both groups was systematically screened for TORCH IgG and IgM during pre-conceptional evaluation and/or at the beginning of pregnancy. The assessment of IgG avidity was also evaluated in order to identify primary infection or false positivity. RESULTS: A significant increase of CMV IgM false positivity in APS in comparison with controls was detected. A worse pregnancy outcome was observed among APS patients having CMV IgM false positivity in comparison with APS patients without false positivity; in particular a statistically significant lower neonatal birth weight and a lower neonatal birth weight percentile were observed. CONCLUSION: Our data suggest that the presence of CMV IgM false positivity could represent a novel prognostic factor for poor pregnancy outcome in APS patients.

Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome.

OBJECTIVE: To investigate the predictive value of serum C3 and C4 complement component levels in relation to pregnancy outcome in patients with antiphospholipid syndrome (APS). MATERIALS AND METHODS: A prospective study of 47 pregnancies associated with APS was performed. Pregnancy outcome was analyzed in terms of: fetal loss, preterm delivery (≤34 gestational weeks), fetal intrauterine growth restriction (IUGR), birth weight <2500 g and preeclampsia. Week at delivery, neonatal birth weight and neonatal birth weight percentile were also investigated. Hypocomplementemia, positivity for anti-dsDNA and triple positivity for antiphospholipid antibodies (aPL) were related to pregnancy outcome. RESULTS: Forty-three pregnancies ended in live births with a fetal loss rate of 8.5%. Fetal death, preterm delivery and birth weight <2500 g were associated with hypocomplementemia (p = 0.019, p = 0.0002, p < 0.0001 respectively). Lower neonatal birth weight, lower neonatal birth weight percentile and lower week at delivery were associated with hypocomplementemia (p < 0.0001, p = 0.0003, p < 0.0001 respectively) and with triple aPL positivity (p = 0.008, p = 0.014, p = 0.03 respectively). A poor pregnancy outcome was confirmed among primary APS (PAPS) pregnancies with hypocomplementemia. Multivariate analysis confirmed that hypocomplementemia was an independent predictor of lower neonatal birth weight (p = 0.0001) and lower week at delivery (p = 0.002). CONCLUSION: Hypocomplementemia could be considered a novel prognostic factor for pregnancy outcome in APS patients.

Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells.

Recent literature highlights the importance of pro-inflammatory cytokines in the biology of breast cancer stem cells (CSCs), unraveling differences with respect to their normal counterparts. Expansion of mammospheres (MS) is a valuable tool for the in vitro study of normal and cancer mammary gland stem cells. Here, we expanded MSs from human breast cancer and normal mammary gland tissues, as well from tumorigenic (MCF7) and non-tumorigenic (MCF10) breast cell lines. We observed that agonists for the retinoid X receptor (6-OH-11-O-hydroxyphenanthrene), retinoic acid receptor (all-trans retinoic acid (RA)) and peroxisome proliferator-activated receptor (PPAR)-γ (pioglitazone (PGZ)), reduce the survival of MS generated from breast cancer tissues and MCF7 cells, but not from normal mammary gland or MCF10 cells. This phenomenon is paralleled by the hampering of pro-inflammatory Nuclear Factor-κB (NF-κB)/Interleukin-6 (IL6) axis that is hyperactive in breast cancer-derived MS. The hindrance of such pathway associates with the downregulation of MS regulatory genes (SLUG, Notch3, Jagged1) and with the upregulation of the differentiation markers estrogen receptor-α and keratin18. At variance, the PPARα agonist Wy14643 promotes MS formation, upregulating NF-κB/IL6 axis and MS regulatory genes. These data reveal that nuclear receptors agonists (6-OH-11-O-hydroxyphenanthrene, RA, PGZ) reduce the inflammation dependent survival of breast CSCs and that PPARα agonist Wy14643 exerts opposite effects on this phenotype.