Prevalence and risk of stillbirth according to biologic vulnerability phenotypes in the municipality of São Paulo, Brazil: A population-based cohort study.

OBJECTIVE: To estimate the prevalence and risk of stillbirths by biologic vulnerability phenotypes in a cohort of pregnant women in the municipality of São Paulo, Brazil, 2017-2019. METHODS: Retrospective population-based cohort study. Fetuses were assessed as small for gestational age (SGA), large for gestational age (LGA), adequate for gestational age (AGA), preterm (PT) as less than 37 weeks of gestation, non-PT (NPT) as 37 weeks of gestation or more, low birth weight (LBW) as less than 2500 g, and non-LBW (NLBW) as 2500 g or more. Relative risks (RR) with robust variance were estimated using Poisson regression. RESULTS: In all 442 782 pregnancies, including 2321 (0.5%) stillbirths, were included. About 85% (n = 1983) of stillbirths had at least one characteristic of vulnerability, compared with 21% (n = 92524) of live births. Fetuses with all three markers of vulnerability had the highest adjusted RR of stillbirth-SGA + LBW + PT (RR 155.00; 95% confidence interval [CI] 136.29-176.30) and LGA + LBW + PT (RR 262.04; 95% CI 206.10-333.16) when compared with AGA + NLBW + NPT. CONCLUSION: Our findings show that the simultaneous presence of prematurity, low birth weight, and abnormal intrauterine growth presented a higher risk of stillbirths. To accelerate progress towards reducing preventable stillbirths, one must identify the circumstances of greatest biologic vulnerability.

Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes.

Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11-13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay.

SARS-CoV-2 Seroconversion and Pregnancy Outcomes in a Population of Pregnant Women Recruited in Milan, Italy, between April 2020 and October 2020.

The possible link between SARS-CoV-2 infection and adverse pregnancy outcomes has so far demonstrated heterogeneous results in terms of maternal, fetal, and neonatal complications. We aim to investigate the correlation between SARS-CoV-2 seroconversion and/or neutralization titer and pregnancy outcomes. We analyzed a population of 528 pregnant women followed up from the first trimester of gestation until delivery. For each woman, we collected a first blood sample between 11 and 13 weeks of gestation and a second sample in the perinatal period (between peripartum and puerperium) to assess the presence of SARS-CoV-2 antibodies and/or microneutralization titer (MN titer). Data on pregnancy outcomes (gestational age at delivery, preterm birth before 34 weeks, hypertensive disorders, gestational diabetes, and abnormal fetal growth) were collected. We observed that serologic status per se is not associated with major pregnancy complications. On the contrary, the MN titer was associated with increased odds of gestational diabetes. Although we mainly reported asymptomatic SARS-CoV-2 infections and the absence of severe maternal and neonatal adverse outcomes, SARS-CoV-2 infection might challenge the maternal immune system and explain the moderate increase in adverse outcome odds.

Objectively assessed sleep-disordered breathing during pregnancy and infant birthweight.

BACKGROUND: Sleep-disordered breathing (SDB) in pregnancy is associated with adverse maternal outcomes. The relationship between SDB and infant birthweight is unclear. This study's primary aim is to determine if objectively measured SDB in pregnancy is associated with infant birthweight. METHODS: We measured SDB objectively in early (6-15 weeks' gestation) and mid (22-31 weeks' gestation) pregnancy in a large cohort of nulliparous women. SDB was defined as an Apnea-Hypopnea Index ≥5 and in secondary analyses we also examined measures of nocturnal hypoxemia. We used a modified Poisson regression approach to estimate relative risks (RR) of large-for-gestational-age (LGA: >90th percentile for gestational age) and small-for-gestational-age (SGA: <10th percentile for gestational age) birthweights. RESULTS: The prevalence of early-pregnancy SDB was nearly 4%. The incidence of mid-pregnancy SDB was nearly 6.0%. The prevalence of LGA and SGA was 7.4% and 11.9%, respectively. Early-pregnancy SDB was associated with a higher risk of LGA in unadjusted models (RR 2.2, 95% CI 1.3-3.5) but not BMI-adjusted models (aRR 1.0, 95% CI 0.6-1.8). Mid-pregnancy SDB was not associated with SGA or LGA. Mid-pregnancy nocturnal hypoxemia (% of sleep time <90% oxygen saturation) and increasing nocturnal hypoxemia from early to mid-pregnancy were associated with a higher risk of LGA in BMI-adjusted models. SDB and nocturnal hypoxemia were not associated with SGA. CONCLUSIONS: SDB in pregnancy was not associated with an increased risk of LGA or SGA birthweight, independent of BMI. Some measures nocturnal hypoxemia were associated with an increase in LGA risk, independent of BMI. ClinicalTrials.gov Registration number NCT02231398.

Etiology and perinatal outcome of periviable fetal growth restriction associated with structural or genetic anomaly.

OBJECTIVE: To investigate the etiology and perinatal outcome of periviable fetal growth restriction (FGR) associated with a structural defect or genetic anomaly. METHODS: This was a retrospective study of singleton pregnancies seen at a referral fetal medicine unit between 2005 and 2018, in which FGR (defined as fetal abdominal circumference ≤ 3rd percentile for gestational age) was diagnosed between 22 + 0 and 25 + 6 weeks of gestation. The study group included pregnancies with periviable FGR associated with a genetic or structural anomaly (anomalous FGR), while the control group consisted of structurally and genetically normal pregnancies with periviable FGR (non-anomalous FGR). Results of genetic testing, TORCH screen and postmortem examination, as well as perinatal outcome, were investigated. RESULTS: Of 255 pregnancies complicated by periviable FGR, 188 were eligible; of which 52 (28%) had anomalous FGR and 136 (72%) had non-anomalous FGR. A confirmed genetic abnormality accounted for 17/52 cases (33%) of anomalous FGR, with trisomy 18 constituting over 50% (9/17; 53%). The most common structural defects associated with FGR were central nervous system abnormalities (13/35; 37%). Overall, 12 (23%) cases of anomalous FGR survived the neonatal period. No differences were found in terms of perinatal survival between pregnancies with anomalous and those with non-anomalous FGR. CONCLUSIONS: Most pregnancies complicated by anomalous FGR were associated with a structural defect. The presence of an associated genetic defect was invariably lethal, while those with a structural defect, in the absence of a confirmed genetic abnormality, survived into infancy in over 90% of cases, with an overall one in three chance of perinatal survival. These data can be used for counseling prospective parents. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Does tea consumption during early pregnancy have an adverse effect on birth outcomes?

BACKGROUND: Tea, a common beverage, has been suggested to exhibit a number of health benefits. However, one of its active ingredients, caffeine, has been associated with preterm birth and low birthweight. We investigated whether tea consumption during early pregnancy is associated with an increased risk of preterm birth and abnormal fetal growth. METHODS: A total of 8775 pregnant women were included from the Born in Guangzhou Cohort Study. Tea consumption (type, frequency, and strength) during their first trimester and social and demographic factors were obtained by way of questionnaires administered during pregnancy. Information on birth outcomes and complications during pregnancy was obtained from hospital medical records. RESULTS: Overall habitual tea drinking (≥1 serving/week) prevalence among pregnant women was low, at 16%. After adjustment for potential confounding factors (eg, maternal age, educational level, monthly income) tea drinking during early pregnancy was not associated with an increased risk of preterm birth or abnormal fetal growth (small or large for gestational age) (P>.05). CONCLUSIONS: We did not identify a consistent association between frequency of tea consumption or tea strength and adverse birth outcomes among Chinese pregnant women with low tea consumption. Our findings suggest that occasional tea drinking during pregnancy is not associated with increased risk of preterm birth or abnormal fetal growth. Given the high overall number of annual births in China, our findings have important public health significance.