Maternal Illness Severity Research Articles

Maternal and neonatal outcomes associated with illness severity of maternal COVID-19.

Several reports demonstrated that perinatal SARS-CoV-2 has significant impact on maternal and neonatal health outcomes. However, the relationship between severity of maternal illness with outcomes remains less clear. This is a single-center retrospective cohort study of mother/infant dyads with positive maternal test for SARS-CoV-2 between 14 days prior and 3 days after delivery from 3/30/2020 to 12/28/2021. Among 538 mothers, those with moderate/severe/critical illness were more likely to undergo induction, receive oxygen, mechanical ventilation or ECMO. Mortality was significantly higher among the mothers with severe illness than asymptomatic and those with mild illness (6% vs 0% and 0%, respectively, P < 0.05). Neonates born to mothers with moderate/severe/critical illness were more likely to be preterm with lower birth weight, and to be admitted to the NICU (P < 0.05) but not to be small for gestational age. Mild maternal illness was only associated with NICU admission for isolation precaution and decreased rate of breastfeeding. Maternal illness severity was significantly associated with prematurity and several adverse maternal and neonatal outcomes.

Association between hospital case volume and maternal adverse events in patients with placental abruption: An analysis using a Japanese national inpatient database.

To clarify the relationship between the prognosis of patients with placental abruption (PA) and the healthcare delivery system using data from a large national inpatient database in Japan. Using the Diagnosis Procedure Combination database, we conducted a retrospective cohort study with the data of patients in almost 1000 hospitals with the primary diagnosis of PA who were hospitalized from April 2014 to March 2021. We divided the hospitals into four groups based on the number of deliveries per month. We performed multilevel logistic regression analysis to analyze the relationship between hospital case volume and maternal end-organ injury (MEOI). Altogether, 8222 patients were included for analysis; among whom, 3575 (44%) were transferred by ambulance. MEOI was noted in 977 patients (12%) with no obvious difference by hospital case volume. Ambulance transfer, age, gestational weeks at admission, delivery on the first day of hospitalization, and history of eclampsia were significantly associated with a higher incidence of MEOI, but the hospital case volume was not. Using a Japanese administrative database, our study shows that hospital case volume was not significantly associated with the severity of maternal illness among patients with PA.

Prenatal antidepressant exposure and emotional disorders until age 22: a danish register study

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22.MethodsWe prospectively followed 1,094,202 single-birth Danish children born 1997–2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997–2003) to further quantify potential residual confounding by subclinical factors.ResultsThe final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7–13] years) versus unexposed (12 [IQR:12–17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes.ConclusionsWhile SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.

Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2: Current Evidence and Perspectives

Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2: Current Evidence and Perspectives

Vaccine Protection Through Placenta and Breastfeeding: The Unmet Topic in COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has turned pregnant women’s healthcare into a worldwide public health challenge. Although initial data did not demonstrate pregnancy as a more susceptible period to severe outcomes of acute severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection, there are an increasing number of reports showing that not only pregnant women might be at significantly higher risk than non-pregnant women by COVID-19 but also the fetus. These findings may be related to adaptive changes that occur during pregnancy, such as the reduction in the residual respiratory capacity, the decrease in viral immune responses, and the increased risk for thromboembolic events. Additionally, despite the SARS-CoV-2 vertical transmission evidence being uncommon, maternal illness severity might reflect serious perinatal and neonatal outcomes. Thus, protecting the maternal–fetal dyad against COVID-19 is critical. Even though pregnant women initially were excluded from vaccine trials, several studies have provided safety and efficacy of the overall vaccine COVID-19 platforms. Vaccination during pregnancy becomes a priority and can generate benefits for both the mother and newborn: maternal neutralizing antibodies are transmitted through the placenta and breastfeeding. Moreover, regarding passive immunization, human milk contains other bioactive molecules and cells able to modulate the newborn’s immune response, which can be amplified after the vaccine. Nonetheless, many issues remain to be elucidated, considering the magnitude of the protective immunity transferred, the duration of the induced immunity, and the optimal interval for pregnant immunization. In this review, we assessed these unmet topics supported by literature evidence regarding the vaccine’s immunogenicity, pregnancy immune heterogeneity, and the unique human milk antiviral features.

Impact of Severity of Maternal COVID-19 Infection on Perinatal Outcome and Vertical Transmission Risk: An Ambispective Study From North India.

BackgroundIn contrast to the first wave, the second COVID-19 wave has taken a huge toll affecting maternal outcomes adversely. The aim of this study was to investigate the consequences of the severity of maternal disease on perinatal outcomes and the risk of vertical transmission and to find out the factors associated with adverse fetomaternal outcomes.Materials and methodsThis was an ambispective observational study including COVID-19 infected pregnant patients; 20-40 years of age irrespective of gestational age admitted at Government Institute of Medical Sciences, UP, India. The patients were divided into two groups: CW 1 (COVID-19 Wave 1): Patients admitted between April 1, 2020 and December 31, 2020 and CW 2 (COVID-19 Wave 2): Patients admitted between April 1, 2021 to May 31, 2021.Data in two groups were compared and analyzed with respect to the clinical profile, laboratory parameters, fetomaternal outcome and the risk of vertical transmission of COVID-19 infection.ResultsWe included 134 eligible patients in the CW1 group and 58 in the CW2 group. Significantly more patients were symptomatic in CW2 (23.1% versus 60.3%, p= <0.001). In CW2, maternal neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP) and D-Dimer were significantly raised along with abnormal chest x-rays. There was a significant increase in maternal mortality in CW2 (1.5% vs 13.7%; p≤0.001).A total of 76 patients delivered in CW1 and 26 in CW2 with increased incidence of cesarean section (43.4%; 42.3%), preterm deliveries (28.2%; 37%) and low birth weight (34.6%; 25.9%) in both waves, the difference among two groups being statistically insignificant. Compared to CW1, perinatal mortality was significantly increased in CW2 (2.2% vs 15.5%; p<0.001). Though nasopharyngeal swab tested positive in four neonates in CW1 and two neonates in CW2, no evidence of vertical transmission was observed even with increased severity of maternal illness. On regression analysis, D-Dimer and CRP were found to have a positive association with maternal and perinatal mortality. ConclusionThe severity of maternal illness proportionately affects the neonatal outcome with no impact on the risk of vertical transmission of infection. D-Dimer and CRP have emerged as independent predictors for maternal and perinatal mortality and hence can be utilized in obstetrics decision-making.

Pregnancy Outcomes Among Women With and Without Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Published data suggest that there are increased hospitalizations, placental abnormalities, and rare neonatal transmission among pregnant women with coronavirus disease 2019 (COVID-19). To evaluate adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. This observational cohort study of maternal and neonatal outcomes among delivered women with and without SARS-CoV-2 during pregnancy was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System (Dallas, Texas), a high-volume prenatal clinic system and public maternity hospital with widespread access to SARS-CoV-2 testing in outpatient, emergency department, and inpatient settings. Women were included if they were tested for SARS-CoV-2 during pregnancy and delivered. For placental analysis, the pathologist was blinded to illness severity. SARS-CoV-2 infection during pregnancy. The primary outcome was a composite of preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate among women delivered after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were described. From March 18 through August 22, 2020, 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 were delivered, including 252 who tested positive for SARS-CoV-2 and 3122 who tested negative. The cohort included 2520 Hispanic (75%), 619 Black (18%), and 125 White (4%) women. There were no differences in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. SARS-CoV-2 positivity was more common among Hispanic women (230 [91%] positive vs 2290 [73%] negative; difference, 17.9%; 95% CI, 12.3%-23.5%; P < .001). There was no difference in the composite primary outcome (52 women [21%] vs 684 women [23%]; relative risk, 0.94; 95% CI, 0.73-1.21; P = .64). Early neonatal SARS-CoV-2 infection occurred in 6 of 188 tested infants (3%), primarily born to asymptomatic or mildly symptomatic women. There were no placental pathologic differences by illness severity. Maternal illness at initial presentation was asymptomatic or mild in 239 women (95%), and 6 of those women (3%) developed severe or critical illness. Fourteen women (6%) were hospitalized for the indication of COVID-19. In a large, single-institution cohort study, SARS-CoV-2 infection during pregnancy was not associated with adverse pregnancy outcomes. Neonatal infection may be as high as 3% and may occur predominantly among asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and hospitalization frequency was similar to rates among nonpregnant women.

Severe early-onset PE with or without FGR in Chinese women

Early-onset preeclampsia (PE) is a severe condition with highest risk of perinatal complications. In current study, we compared PE severity, laboratory results and placental pathological lesions between early-onset PE with fetal growth restriction (PE + FGR) and appropriate gestational age (PE + AGA) neonates, with the aim to identify potential maternal risk factors associated with FGR. A retrospective case study was conducted in 304 PE women, and 31 cases with mild PE were excluded. 276 patients with severe PE were divided into PE + FGR (163, 59.1%) and PE + AGA (113, 40.9%) groups and underwent clinical analysis. 244 cases were further submitted for pathologic examinations to compare the differences of placental lesions between these two groups. As compared to PE + AGA, the maternal pre-pregnancy BMI (P = 0.003) and the rate of anemia (P = 0.004) were lower in PE + FGR; while the rate of severe low serum albumin (P = 0.020) was higher. Moreover, severe low serum albumin level (aOR = 2.43, P = 0.046) and abnormal uric acid (aOR = 2.19, P = 0.033) were positively correlated to the incidence of FGR, while pre-pregnancy BMI (aOR = 0.39, P = 0.001) and anemia (aOR = 0.33, P = 0.001) showed negative correlation. The placental examinations further showed positively correlation between chronic villitis (aOR = 4.32, P = 0.028) and FGR. Surprisingly, general measures of maternal illness severity failed to present any significant correlation to FGR, except for blood pressure, which showed negative correlation. For the first time, we studied a relatively large case series of Chinses early-onset PE women, and identified multiple factors associated with FGR incidence. Our study provided some opinions on clinal diagnosis and treatment for early-onset PE with FGR.

Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system.

Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease-specificity of this risk has not been addressed and possibility of confounding has not been excluded. Children with ASD or attention deficit-hyperactivity disorder (ADHD) delivered in a large New England health care system were identified from electronic health records, and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and electronic health records to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1,377 children diagnosed with ASD and 2,243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression [OR 1.10 (0.70–1.70)]. Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression [OR 1.81 (1.22–2.70)]. These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.

A register study of the impact of stopping third trimester selective serotonin reuptake inhibitor exposure on neonatal health

To determine whether risk for adverse neonatal outcomes are reduced by stopping SSRI use before the end of pregnancy. Using population health data, maternal health and prenatal SSRI prescriptions were linked to neonatal birth records (N = 119,547) (1998-2001). Neonates SSRI-exposed in the last 14 days (L14) of gestation were compared with infants who had gestational exposure, but not during the last 14 days (NL14). Propensity score matching was used to control for potential confounders (total exposure, maternal health characteristics). Increased risk for neonatal respiratory distress was present where L14 exposure occurred compared with risk where exposure stopped before L14. However, controlling for potential maternal and neonatal confounders, differences disappeared. Controlling for maternal illness severity, reducing exposure to SSRI's at the end of pregnancy had no significant clinical effect on improving neonatal health. These findings raise the possibility that some adverse neonatal outcomes may not be an acute pharmacological condition such as toxicity or withdrawal.

Early pregnancy azathioprine use and pregnancy outcomes

Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness.

Digest

Digest

Mood Stabilizer Discontinuation in Pregnant Women With Bipolar Disorder

Back to table of contents Previous article Next article Letters to the EditorFull AccessMood Stabilizer Discontinuation in Pregnant Women With Bipolar DisorderCARRIE MAZER-POLINE D.O.ARTHUR RIFKIN , M.D.STEPHEN GEISLER M.D.TINA WALCH M.D.,CARRIE MAZER-POLINE D.O.Search for more papers by this authorARTHUR RIFKIN , M.D.Search for more papers by this authorSTEPHEN GEISLER M.D.Search for more papers by this authorTINA WALCH M.D.Search for more papers by this author,Published Online:1 May 2008https://doi.org/10.1176/appi.ajp.2008.08010036AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: In their article, Dr. Viguera et al. concluded that the overall risk of at least one recurrence of a new mood episode during pregnancy was 71% among women who discontinued the use of a mood stabilizer 6 months prior to conception to 12 weeks postconception (relative to women who continued treatment with a mood stabilizer). As indicated in the article, the two groups of women differed with regard to several characteristics.In the multivariate modeling or risk-factors-adjusted analysis, only some of the predictors of recurrence were included. It is not clear to us whether all the statistically significant predictors were covaried. For example, rapid cycling, which is a predictor of recurrence, was not entered as a covariate, although it did differ between the two groups at baseline.We are also puzzled by the way the authors presented the issue of current adjunctive antipsychotic use. There was a large difference between the two groups of women. The use of current adjunctive antipsychotics was reported in 21% of subjects who discontinued the use of a mood stabilizer and in 41% of those who continued treatment. This difference is close to significance (p=0.07). The list of predictors of recurrence did not include the adjunctive use of antipsychotics, nor was it mentioned whether adjunctive use was associated with the risk of recurrence. Given the likelihood that antipsychotics may be mood stabilizers, should not this factor have received attention in the data analysis?Additionally, it would be necessary to know which subjects discontinued the use of a mood stabilizer more than 1 month prior to conception, since the natural course of the illness would likely suggest that the longer period of time an individual is medication free, the higher the likelihood of recurrence. It can be hypothesized that if the data analysis had taken into consideration the length of time since discontinuation, the results might have shown that discontinuing the use of a mood stabilizer close to conception may produce different recurrence rates.Symptoms of change in energy level, appetite, concentration, and psychomotor retardation may all occur in normal, healthy pregnancies and may not be associated with major depression. How did the analysis adjust for this potential confounder? This may explain the much greater frequency of depressive episodes relative to manic episodes. In addition, the nature of a woman’s previous episode may predict the type of relapse experienced during pregnancy.Finally, were there any untoward conditions in the newborn children that were part of this study? For many clinicians, the recommendation whether to discontinue or continue medication during the first trimester is influenced not only by the severity of maternal illness but also the perceived risk to the exposed fetus.Glen Oaks, N.Y.Drs. Mazer-Poline, Rifkin, and Walch report no competing interests. Dr. Geisler has served on the speakers bureaus of Pfizer and AstraZeneca.This letter (doi: 10.1176/appi.ajp.2008.08010036) was accepted for publication in February 2008. FiguresReferencesCited byDetailsCited ByNone Volume 165Issue 5 May, 2008Pages 646-647THE AMERICAN JOURNAL OF PSYCHIATRY May 2008 Volume 165 Number 5 Metrics PDF download History Published online 1 May 2008 Published in print 1 May 2008

Neonatal Outcomes After Prenatal Exposure to Selective Serotonin Reuptake Inhibitor Antidepressants and Maternal Depression Using Population-Based Linked Health Data

Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants and maternal depression both alter neonatal health, and distinguishing the effects of each influence remains challenging. To determine whether exposure to SSRIs and depression differs from exposure to maternal depression alone. Using population health data, records of neonatal birth outcomes were linked to records of maternal health and prenatal maternal prescriptions for SSRIs. Population of British Columbia, Canada. Mothers and their infants, representing all live births during a 39-month period (N = 119,547) (1998-2001). Outcomes from infants of depressed mothers treated with SSRIs (SE-D) were compared with outcomes from infants of depressed mothers not treated with medication (DE) and nonexposed controls. To control for maternal mental illness severity, propensity score matching was used to identify a comparison group of DE mothers who were similar to the SE-D mothers in characteristics in the year preceding and during pregnancy. Fourteen percent of mothers were diagnosed as having depression during their pregnancy, and the incidence of prenatal SSRI exposure increased from 2.3% to 5.0% during a 39-month period. Birth weight and gestational age for SE-D infants were significantly less than for DE infants, as was the proportion of infants born at less than 37 weeks (95% confidence interval [CI], -1 to -64, -0.25 to -0.45, and -0.009 to -0.04, respectively), although differences in the incidence of birth weight less than the 10th percentile for gestational age were not significant. An increased proportion of SE-D infants had neonatal respiratory distress (13.9% vs 7.8%), jaundice (9.4% vs 7.5%), and feeding problems (3.9% vs 2.4%) compared with DE infants (95% CI of difference, 0.042-0.079, 0.003-0.334, and 0.005-0.025, respectively). When outcomes were compared between SE-D and propensity score-matched DE neonates, SE-D was associated with increased incidence of birth weight below the 10th percentile and rates of respiratory distress. With linked population health data and propensity score matching, prenatal SE-D exposure was associated with an increased risk of low birth weight and respiratory distress, even when maternal illness severity was accounted for.

Enterovirus infections.

Enterovirus infections.

Management of asymptomatic neonates with prolonged rupture of membranes.

Guidelines for management of asymptomatic term and preterm neonates born to mothers with prolonged rupture of membranes (PROM) have not been clearly established. A survey was conducted to identify current management practice of neonatologists in midwestern states and to find if there is consensus among physicians with regard to management of PROM without chorioamnionitis, with chorioamnionitis but without treatment prior to delivery, and with intrapartum maternal antibiotic therapy prior to delivery. One hundred thirty seven responses to the questionnaire were received. Management of asymptomatic at risk neonates varied in different clinical scenarios. Preterm neonates were screened (94% vs 82%, p < 0.001) and treated (64% vs 41%, p < 0.001) more often than term babies. In the absence of maternal symptoms of chorioamnionitis, term neonates were usually observed or treated based on screening test results. With maternal symptoms, 94% of physicians ordered screening test. Prematurity and perceived severity of maternal illness significantly influenced the decision to treat routinely irrespective of screening test results. Physicians favour routine treatment of infants born to mothers who had received intrapartum antibiotic therapy; opinion was divided about management of term asymptomatic infant born to mothers with chorioamnionitis without intrapartum antibiotic therapy. Lumbar punctures were not routinely done for term or preterm neonates prior to antibiotic therapy. Further studies are needed to answer questions regarding the benefits and risks of routine therapy of high risk neonates vs routine clinical observation and selective therapy of only infants who develop symptoms.

Intelligence of Children Whose Mothers Have Biliary Tract Disease

The intelligence of children whose mothers had cholecystectomies for cholelithiasis, with or without cholecystitis, was compared to the intelligence of control children. Within the group with maternal biliary-tract disease a correlation between severity of maternal illness and IQ of the child was found. The speculation was proffered that the availability of linoleic acid for fetal brain development might be decreased in pregnant women who had biliary tract disease.