Risk Of Adverse Perinatal Outcomes Research Articles

European association of perinatal medicine (EAPM) position statement: Screening, diagnosis and management of congenital anomalies of the umbilical cord

Congenital anomalies of the umbilical cord are associated with an increased risk of pregnancy and perinatal complications. Some anomalies of the cord have a higher prevalence than other fetal structural anomalies. The most common anomalies are the absence of an umbilical artery and velamentous insertion of the cord (with or without vasa previa). These anomalies, even when not associated with fetal structural defects, increase the risk of adverse perinatal outcome including, fetal growth restriction and stillbirth. In the absence of prenatal diagnosis, vasa previa is associated with the highest perinatal morbidity and mortality of all congenital anomalies of the umbilical cord. Most cases can be detected by ultrasound from the beginning of the second trimester and should be included in the routine mid-pregnancy ultrasound examination. Documentation should include cord insertion site, number of vessels in the cord, and if other pathologies have been detected. Pregnancies at increased risk of velamentous cord insertion should be screened for vasa previa using transvaginal ultrasound and colour Doppler imaging. If a velamentous cord insertion or isolated single umbilical artery is detected, individualised follow-up during pregnancy and tailored obstetric management are indicated.

The Association Between Unintended Pregnancy and Perinatal Outcomes in Low-Risk Pregnancies: A Retrospective Registry Study in the Netherlands.

People with unintended pregnancies might be at increased risk of adverse perinatal outcomes due to structural factors, distress, or delayed prenatal care. Existing studies addressing this association yielded inconsistent findings. Using contemporary data from a large Dutch midwifery care registry, we investigated the association between unintended pregnancy ending in birth and neonatal outcomes, parental morbidity, and obstetric interventions. We extend previous research by exploring whether delayed initiation of prenatal care mediates these associations. This study used data (N = 9803) from a Dutch nationally representative registry of people with low-risk pregnancies receiving primary midwife-led care in the Netherlands between 2012 and 2020. Using logistic (mediation) regression analyses adjusted for potential confounders we investigated associations between unintended pregnancy and neonatal outcomes (low Apgar score, small for gestational age, and prematurity), parental morbidity (hypertension and gestational diabetes mellitus), and obstetric interventions (induction of labor, pain medication, assisted vaginal birth, and cesarean birth) and whether delayed initiation of prenatal care mediated these associations. Unintended pregnancies were associated with increased odds of low Apgar scores (odds ratio [OR], 1.68; 95% CI, 1.09 -2.59), preterm birth (OR, 1.27; 95% CI, 1.02-1.58), small for gestational age (OR, 1.19; 95% CI, 1.00-1.41), and induction of labor (OR, 1.14; 95% CI, 1.01-1.28). Conversely, unintended pregnancy was associated with a decreased odds of cesarean birth (OR, 0.83; 95% CI, 0.71-0.97). The timing of prenatal care initiation did not mediate any of these associations. Our findings suggest that people in primary midwifery-led care with unintended pregnancies ending in birth are at increased risk for adverse perinatal health outcomes and that structural factors might underlie this link. Health care professionals and policy makers should attend to their own biases and offer nonjudgmental, tailored preventive preconception care and antenatal care strategies for people with higher vulnerabilities.

Impact of Thrombophilic Polymorphisms in Antenatal Women on Perinatal Health: A Single-Center Prospective Study.

Despite pregnancy's hypercoagulable state, the correlation between inherited thrombophilia and thrombotic adverse pregnancy outcomes remains uncertain. The objective of this study was to determine the prevalence of inherited thrombophilic polymorphisms among asymptomatic pregnant individuals and to examine their potential correlation with adverse perinatal outcomes. in this single-center prospective study, 105 healthy pregnant women were included. Genotyping was conducted for factor V Leiden (FVL), prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and plasminogen activator inhibitor-1 (PAI-1), alongside the assessment of protein C (PC), protein S (PS), and antithrombin (AT) levels. The study analyzed the association between inherited thrombophilic polymorphisms and pregnancy complications linked to placental insufficiency, such as gestational hypertension (GH), preeclampsia (PE), intrauterine death (IUD), fetal growth restriction (FGR), and placental abruption. The prevalence of identifiable thrombophilic polymorphism mutations was 61.9% (95% confidence interval-CI 52.4-70.8%), with the most common single mutation being PAI-1 4G/5G (12/105, 11.4%, 95% CI 6.4-18.5). The most frequent combined mutation was heterozygosity for MTHFR C677T and PAI-1 (12/105, 11.4%, 95% CI 6.4-18.5). Notably, no FVL homozygous carriers or single homozygous and heterozygous carriers for prothrombin polymorphisms were found. Additionally, no deficiencies in PC and AT were detected among participants. Except for homozygosity for PAI-1, none of the studied polymorphisms demonstrated a significant association with pregnancy complications linked to placental insufficiency. The asymptomatic carriers of inherited thrombophilic polymorphisms do not have an increased risk of adverse perinatal outcomes.

Vitamin D status of pregnant women with obesity in the UK and its association with pregnancy outcomes: a secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) study.

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial, we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI ≥ 30 kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17 ± 1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum 25-hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67 % had 25(OH)D < 50 nmol/l and 26 % had concentrations < 25 nmol/l. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95 % CI: -39, -27), Asian (% difference = -43; 95 % CI: -51, -35) and other non-White (% difference = -26; 95 % CI: -35, -14) ethnicity compared with women of White ethnicity (n 1086; P < 0·001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D < 25 nmol/l compared with ≥ 50 nmol/l (OR = 1·58; 95 % CI: 1·09, 2·31), but the magnitude of effect estimates was attenuated in the multivariable model (OR = 1·33; 95 % CI: 0·88, 2·00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth or small for gestational age or large-for-gestational-age delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.

Overexpression of Connexin 40 in the Vascular Endothelial Cells of Placenta with Acute Chorioamnionitis.

Connexins (Cx) 43 and 40 play a role in leukocytes recruitment in acute inflammation. They are expressed in the endothelial cells. They are also found in the placenta and involved in the placenta development. Acute chorioamnionitis is associated with an increased risk of adverse perinatal outcomes. The aim of this study was to determine the expressions of Cx43 and Cx40 in the placenta of mothers with acute chorioamnionitis, and to correlate their association with the severity of chorioamnionitis and adverse perinatal outcomes. This study comprised a total of 81 cases, consisting of 39 placenta samples of mothers with acute chorioamnionitis and 42 non-acute chorioamnionitis controls. Cx43 and Cx40 immunohistochemistry were performed on all cases and their expressions were evaluated on cytotrophoblasts, syncytiotrophoblasts, chorionic villi endothelial cells, stem villi endothelial cells, maternal endothelial cells and decidua of the placenta. Primigravida has a significantly higher risk of developing acute chorioamnionitis (p < 0.001). Neonates of mothers with a higher stage of fetal inflammatory response was significantly associated with lung complications (p = 0.041) compared to neonates of mothers with a lower stage. The expression of Cx40 was significantly higher in fetal and maternal vascular endothelial cells in acute chorioamnionitis (p < 0.001 and p = 0.037, respectively) compared to controls. Notably, Cx43 was not expressed in most of the types of cells in the placenta, except for decidua. Both Cx43 and Cx40 expressions did not have correlation with the severity of acute chorioamnionitis and adverse perinatal outcomes. Cx40 was overexpressed in the fetal and maternal vascular endothelial cells in the placenta of mothers with acute chorioamnionitis, and it may have a role in the development of inflammation in placenta.

Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment.

Pregnancy complicated by obesity represents an increased risk of unfavorable perinatal outcomes such as gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, preterm birth, and impaired fetal growth, among others. Obesity is associated with deficiencies of micronutrients, and pregnant women with obesity may have higher needs. The intrauterine environment in pregnancies complicated with obesity is characterized by inflammation and oxidative stress, where maternal nutrition and metabolic status have significant influence and are critical in maternal health and in fetal programming of health in the offspring later in life. Comprehensive lifestyle interventions, including intensive nutrition care, are associated with a lower risk of adverse perinatal outcomes. Routine supplementation during pregnancy includes folic acid and iron; other nutrient supplementation is recommended for high-risk women or women in low-middle income countries. This study is an open label randomized clinical trial of parallel groups (UMIN Clinical Trials Registry: UMIN000052753, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000060194) to evaluate the effect of an intensive nutrition therapy and nutrient supplementation intervention (folic acid, iron, vitamin D, omega 3 fatty acids, myo-inositol and micronutrients) in pregnant women with obesity on the prevention of GDM, other perinatal outcomes, maternal and newborn nutritional status, and infant growth, adiposity, and neurodevelopment compared to usual care. Given the absence of established nutritional guidelines for managing obesity during pregnancy, there is a pressing need to develop and implement new nutritional programs to enhance perinatal outcomes.

Clomiphene citrate administered in peri-conception phase causes fetal loss and developmental impairment in mice.

Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated in mice the consequences for fetal development and pregnancy outcome of peri-conception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 h after mating was seen, with a moderate dose of 0.75 mg/kg sufficient to cause altered reproductive outcomes in three independent cohorts. Viable pregnancy was reduced by 30%, late gestation fetal weight was reduced by 16%, and ∼30% of fetuses exhibited delayed development and/or congenital abnormalities not seen in control dams, including defects of the lung, kidney, liver, eye, skin, limbs, and umbilicus. Clomiphene citrate also caused a 30 h average delay in time of birth, and elevated rate of pup death in the early postnatal phase. In surviving offspring, growth trajectory tracking and body morphometry analysis at 20 weeks of age showed post-weaning growth and development comparable to controls. A dysregulated inflammatory response in the endometrium was observed and may contribute to the underlying pathophysiological mechanism. These results demonstrate that in utero exposure to clomiphene citrate during early pregnancy can inhibit implantation and impact fetal growth and development, causing adverse perinatal outcomes. The findings raise the prospect of similar iatrogenic effects in women where clomiphene citrate may be present in the peri-conception phase unless its use is well-supervised.

Risk of adverse perinatal outcomes among African-born Black women in California, 2011-2020.

African-born women have a lower risk of preterm birth and small for gestational age (SGA) birth compared to United States (US)-born Black women, however variation by country of origin is overlooked. Additionally, the extent that nativity disparities in adverse perinatal outcomes to Black women are explained by individual-level factors remains unclear. We conducted a population-based study of non-anomalous singleton live births to US- and African-born Black women in California from 2011-2020 (n=194,320). We used age-adjusted Poisson regression models to estimate risk of preterm birth and SGA, and reported risk ratios (RR) and 95% confidence intervals (CI). Decomposition using Monte Carlo integration of the g-formula computed the percentage of disparities in adverse outcomes between US- and African-born women explained by individual-level factors. Eritrean women (RR 0.4; 95%CI: 0.3, 0.5) had the largest differences in risk of preterm birth and Cameroonian women (RR 0.5; 95% CI: 0.3, 0.6) in SGA birth, compared to US-born Black women. Ghanaian women had smaller differences in risk of preterm birth (RR 0.8; 95%CI: 0.7, 1.0) and SGA (RR 0.9; 95% CI 0.8, 1.1) compared to US-born women. Overall, we estimate that absolute differences in socio-demographic and clinical factors contributed to 32% of nativity-based disparities in the risk of preterm birth and 26% of disparities in SGA. We observed heterogeneity in risk of adverse perinatal outcomes for African- compared to US-born Black women, suggesting that nativity disparities in adverse perinatal outcomes were not fully explained by differences in individual-level factors.

The correlation between serum total bile acid and adverse perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP) and non-ICP hypercholanemia of pregnancy.

The association between excessive serum total bile acid (TBA) and adverse perinatal outcomes in individuals with non-intrahepatic cholestasis of pregnancy (non-ICP) hypercholanemia has not been determined, and it is unclear if this link is similar to that observed in patients with ICP. To examine the adverse perinatal outcomes in two specific subcategories: those with ICP and those with non-ICP, including individuals with liver disease and asymptomatic hypercholanemia of pregnancy (AHP), at different levels of TBA. Investigate the correlation between TBA levels and adverse perinatal outcomes of ICP, liver disease, and AHP. From 2013 to 2021, pregnant women with excessive TBA levels were taken from the electronic medical record database of our hospital and categorized into three groups: ICP (n = 160), liver disease (n = 164), and AHP (n = 650). This was done as part of a retrospective cohort research project. Multivariable regression and subgroup analyses were performed to examine the association between TBA levels and adverse perinatal outcomes in each group. The study found no significant differences in adverse perinatal outcomes between the ICP and liver disease groups at different TBA levels. However, at moderate TBA levels, both groups had a higher risk of adverse perinatal outcomes than the AHP group (p < 0.017). Among liver disease cases with TBA ≥ 100µmol/L, three cases of perinatal deaths (6.67%) associated with moderate-to-severe acute hepatitis occurred between 27 and 33 weeks of gestation. A 59% higher chance of perinatal death was found for every 10 µmol/L rise in TBA, even after significant variables and confounders were taken into account (adjusted odds ratio (aOR) = 1.59; 95% confidence interval (CI): 1.06-2.40; p = 0.03). If a pregnant woman has moderate-to-severe liver disease and TBA ≥ 100µmol/L, preterm termination of pregnancy (before 34 weeks) may be considered.

Incidence of Adverse Perinatal Outcomes among Women Exposed to Maternal Near-Misses in Arsi Zone in Ethiopia: Prospective Cohort Study in 2022.

Exposure to maternal near-misses has a massive effect on adverse perinatal outcomes. Hence, investigating the effect of maternal near-misses on perinatal outcomes can aid in the reduction of perinatal morbidity and mortality. The study is aimed at assessing the incidence of adverse perinatal outcomes among women exposed to maternal near-misses at Arsi Zone public hospitals in Ethiopia in 2022. The study included a prospective cohort of 335 women at Arsi Zone public hospitals from December 2021 to June 2022. Women who were admitted for management of pregnancy were followed. The exposed group was women with maternal near-misses screened based on disease-validated criteria. The nonexposed group was made up of women who delivered without complications. Trained data collectors used pretested, structured questionnaires to collect data from women. Pertinent data was also extracted from the clients' logbooks. Data was transferred from EpiData version 3.1 to SPSS version 25 for analysis, logistic regression was computed, and 95% confidence intervals were declared at a p value of 5% significance level. The incidence of adverse perinatal outcomes was higher in the exposed women than in the nonexposed women (56% versus 16%). Contrasted with the nonexposed, women exposed to maternal near-misses had a higher incidence of stillbirth (22% vs. 0.5%), low birth weight (13% vs. 3%), and preterm birth (12% vs. 2%). After adjusting for confounders, exposed women had a twofold increased risk of adverse perinatal outcomes compared to nonexposed women. Delivery mode, delay in seeking care, transport mode, and delay in receiving treatment were the risk factors for negative pregnancy outcomes. In exposed women, a higher incidence of adverse perinatal outcomes was linked to aforementioned risk factors. Evidence-based practice intended to decrease delays in providing maternal care services does indeed improve perinatal outcomes.

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis

The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality. We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825. Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2=0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2=0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2=0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA. We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy. None.

The IRELAnD study—investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial

Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials. The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus. A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis. From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance. In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.

Risk of adverse perinatal outcomes among women with clinical and subclinical histopathological chorioamnionitis.

Histologic chorioamnionitis (HCA) is a placental inflammatory condition associated with adverse perinatal outcomes (APOs). This historical cohort study explores the risk of APOs in pregnant women with HCA and compares the impact of clinical chorioamnionitis (CCA) with subclinical chorioamnionitis (SCCA). Placentas were evaluated by a perinatal pathologist tand all women with HCA were included. Two groups were integrated: (1) women with clinical chorioamnionitis (CCA) and (2) women with subclinical chorioamnionitis (SCCA). Additionally, we conducted a secondary analysis to compare the prevalence of APOs among stage 1, 2 and 3 of HCA and the risk of APOs between grades 1 and 2 of HCA. The APOs analyzed were preterm birth, stillbirth, neonatal weight < 1,500 g, neonatal sepsis. Relative risk with 95% confidence interval was calculated. The study included 41 cases of CCA and 270 cases of SCCA. The mean gestational age at diagnosis and birth was 30.2 ± 5.4 weeks and 32.5 ± 5.1 weeks, for group 1 and 2, respectively. The study also found that women with HCA stage 3 and grade 2 had a higher prevalence and risk of adverse perinatal outcomes. The findings of this study suggest the importance of placental histological study to excluded SCCA, which represents a significant risk to both maternal and neonatal health, contributing to high morbidity and mortality.

The risk of Type 1 diabetes in children born after ART: a Nordic cohort study from the CoNARTaS group.

Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART? The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment. ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life. A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994-2014), Finland (1990-2014), and Norway (1984-2015). The study included 76184 liveborn singletons born after ART and 4403419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively. The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders. During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011-2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group. The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10-14 years, hence a longer follow-up would benefit all analyses and, in particular, the subgroup analyses. Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally. This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. None of the authors has any conflicts of interest to declare regarding this study. ISRCTN11780826.

Obstetric and neonatal outcomes in pregnant women with idiopathic polyhydramnios: a systematic review and meta-analysis

Although the assessment of the amniotic fluid volume in pregnancy is part of the fetal wellbeing surveillance, the impact of idiopathic polyhydramnios (IP) on maternal and perinatal outcomes in unknown. The aim of this meta-analysis was to investigate the association of IP with different maternal and perinatal outcomes. We screened five electronic databases until December 2023 and performed data extraction and quality assessment using ROBINS-E in duplicates. Pooled risk ratios and 95% confidence intervals (95% CI) were calculated with a random effects model. 38 studies were included. Patients with IP were at increased risk of perinatal complications including preterm delivery (RR 1.96, 95% CI 1.35–2.86; I2 = 92%), placental abruption (RR 3.20, 95% CI 2.20–4.65; I2 = 2%), delivery via caesarean section (RR 1.60, 95% CI 1.39–1.84; I2 = 95%) and postpartum haemorrhage (RR 1.98, 95% CI 1.22–3.22; I2 = 84%). Similarly, IP was associated with increased risk of adverse perinatal outcomes including low APGAR score (RR 3.0, 95% CI 1.23–7.35; I2 = 95%), stillbirth (RR 4.75, 95% CI 2.54–8.86; I2 = 9%) and perinatal mortality (RR 4.75, 95% CI 2.67–8.48; I2 = 37%). This meta-analysis suggests that pregnant women with IP may be at increased risk of perinatal complications and adverse neonatal outcomes. However, data remains inconclusive considering the low quality and high heterogeneity of included studies.PROSPERO registration number: CRD42022359944.

Co-occurrence of mental illness and substance use among US pregnant individuals, 2012-2021

AimSubstance use disorders are increasingly prevalent among pregnant individuals, with evident risks of adverse perinatal outcomes. This study examines substance use (tobacco, alcohol and marijuana) among pregnant individuals with mental illness. MethodsA national representative sample of pregnant individuals were derived from 2012 to 2021 National Survey of Drug Use and Health data. Associations of past-year mental illness with past-month polysubstance use and each substance use were analyzed by logistic regression models, with complex sampling weights and survey year. ResultsAmong 6801 pregnant individuals, 16.4% reported having any mental illness (AMI) in 2012 and 2013, increasing to 23.8% in 2020–2021; and SMI increased from 3.3% to 9.4%. Polysubstance use increased disproportionately among those with severe mental illness (SMI), from 14.0% to 18.6%. Pregnant individuals with greater severity of mental illness had higher odds of polysubstance use (Adjusted Odds Ratio, 95% CI: AMI but no SMI vs. without AMI: 1.59 [1.04, 2.44]; SMI vs. without AMI: 5.48 [2.77, 10.82]). ConclusionsPregnant individuals with greater severity of mental illness were more likely to engage in substance use. Evidence-based educational, screening and treatment services, and public policy changes are warranted to mitigate the harmful health outcomes of substance use among US pregnant individuals with mental illness.

Complex umbilical cord entanglement: A case report

Background: Complex umbilical cord entanglement occurs less frequently and is associated with an increased risk of adverse perinatal outcomes. It is associated with umbilical artery pH and base excess levels that are significantly unfavorable, higher incidence of nonreassuring fetal heart rate, meconium-stained amniotic fluid, neonatal intensive care unit admissions, emergency cesarean section, and stillbirth. Case presentation: A 44-year-old para 2+0 gravida 3, with 2 previous cesarean delivery scars at 35 weeks presented with a history of reduced fetal movements for 24 hours. She had attended two antenatal care visits. Her blood group was A, rhesus negative, with hemoglobin levels of 11.2 g/dl, and normal platelets. Urinalysis and serology for HIV, hepatitis B, and Venereal Disease Research Laboratory test were nonreactive. She had received anti-D prophylaxis after her previous deliveries. An urgent obstetric ultrasound scan showed features consistent with intrauterine fetal death. Her coagulation profile was within the normal range. She was admitted for hysterotomy. Intraoperatively, a fresh stillborn baby boy was extracted with a cord around the neck tightly twice and entangled around the trunk. Conclusion: Complex umbilical cord entanglement occurs less frequently and associated with an increased risk of adverse perinatal outcomes. The risk of adverse perinatal outcomes increases with ≥3 loops of the umbilical cord. It is important to look out for cord entanglement antenatally by ultrasonography, particularly when assessing cases of decreased fetal movements.

Life Stressors and Mental Well-Being: Experiences of African American Women Navigating Perinatal Loss and Pregnancy Subsequent to Loss

Historically, African American women have faced racial disparities in perinatal and neonatal mortality rates. There is limited research on the sustained stress and amplified emotional and psychological strain that African American women undergo during perinatal loss. Studies are even scarcer concerning the heightened emotional and psychological difficulties during pregnancies subsequent to loss. Semi-structured interviews were carried out with 22 African American women who had experienced perinatal loss and were either pregnant or had given birth after their loss. Descriptive coding and thematic analysis served in analyzing the data, revealing three main themes: life stressors, mental health complexities, and coping strategies. The results highlighted an increased risk of adverse perinatal outcomes due to social determinants, including income, access to healthcare, and housing. Furthermore, systemic racism exacerbated psychological distress after perinatal loss, often manifesting as depression and anxiety. The study reveals the urgent need to dismantle systemic racism in maternity and mental healthcare to boost perinatal outcomes for African American women. It provides essential insights for developing effective support programs.

Caution: Benzodiazepines in Pregnancy and Risk of Adverse Perinatal Outcomes

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COVID-19 vaccination during pregnancy and adverse perinatal outcomes: a systematic review and meta-analysis.

We aimed to estimate the associations between coronavirus disease 2019 (COVID-19) vaccination during pregnancy and the risks of adverse perinatal outcomes. We performed a literature search in PubMed, Web of Science and Embase to identify eligible studies published up to 24 September 2023, yielding 39 included studies. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random effects model. The pooled results showed that COVID-19 vaccination during pregnancy (any type or dose of COVID-19 vaccination during any trimester) was not associated with an increased risk of adverse perinatal outcomes. In particular, COVID-19 vaccination in the third trimester was associated with a decreased risk of preterm birth (<37weeks) (RR 0.85 [95% CI 0.74 to 0.98]), 5-min Apgar <7 (RR 0.87 [95% CI 0.78 to 0.97]) and neonatal intensive care unit (NICU) admission (RR 0.90 [95% CI 0.86 to 0.95]). The inverse associations were also found in analysis of one-dose vaccination during pregnancy and the risk of miscarriage (RR 0.83 [95% CI 0.72 to 0.96]) and preterm birth (<37weeks) (RR 0.90 [95% CI 0.80 to 1.00]) and two-dose vaccination during pregnancy and the risk of NICU admission (RR 0.86 [95% CI 0.76 to 0.96]). COVID-19 vaccination during pregnancy does not increase the risk of negative outcomes for the mother or baby.