SARS-CoV-2 infection by trimester of pregnancy and adverse perinatal outcomes: a Mexican retrospective cohort study.

OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.

Ultrasonographic assessment of abnormal fetal growth related to uteroplacental-fetal biometrics and Doppler (U-AID) indices: Protocol for multicenter retrospective cohort study trial.

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups.

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

INTRODUCTION: SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth. MATERIALS & METHODS: CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile. RESULTS: Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively. CONCLUSION: FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

Timing of selective serotonin reuptake inhibitor use and risk for preterm birth and related adverse events: with a consideration of the COVID-19 pandemic period.

OBJECTIVE: There is uncertainty around the safety of SSRIs for treating depression during pregnancy. Nevertheless, the use of SSRIs has been gradually increasing, especially during the COVID-19 pandemic period. We aimed to (1) characterize maternal depression rate and use of SSRIs in a recent 10-year period, (2) address confounding by indication, as well as socioeconomic and environmental factors, and (3) evaluate associations of the timing of SSRI exposure in pregnancy with risk for preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) infants among women with depression before pregnancy. METHODS: We conducted propensity score-adjusted regression to calculate odds ratios (ORs) of PTB, LBW, and SGA. We accounted for maternal/pregnancy characteristics, comorbidity, depression severity, time of delivery, social vulnerability, and rural residence. RESULTS: There were 50.3% and 40.3% increases in the prevalence rate of prenatal depression and prenatal SSRI prescription rate during the pandemic. We identified women with depression ≤180 days before pregnancy (n = 8406). Women with no SSRI order during pregnancy (n = 3760) constituted the unexposed group. The late SSRI exposure group consisted of women with an SSRI order after the first trimester (n = 3759). The early-only SSRI exposure group consisted of women with SSRI orders only in the first trimester (n = 887). The late SSRI exposure group had an increased risk of PTB of OR = 1.5 ([1.2,1.8]) and LBW of OR = 1.5 ([1.2,2.0]), relative to the unexposed group. Associations between late SSRI exposure and risk of PTB/LBW were similar among a subsample of patients who delivered during the pandemic. CONCLUSIONS: These findings suggest an association between PTB/LBW and SSRI exposure is dependent on exposure timing during pregnancy. Small for gestational age is not associated with SSRI exposure.

Causal association between rheumatoid arthritis and pregnancy loss and intrauterine growth retardation: A bidirectional two-sample Mendelian randomization study.

OBJECTIVE: To investigate the causal relationship between rheumatoid arthritis (RA) and pregnancy loss and intrauterine growth retardation (IUGR) using Mendelian randomization (MR). METHODS: Genetic variants associated with RA (12,555 cases and 240,862 controls), miscarriage (1475 cases and 149,622 controls), and IUGR (3558 cases and 207,312 controls) were obtained from the FinnGen consortium, and supplementary data on RA (5201 cases and 457,732 controls) and miscarriage (7069 cases and 250,492 controls) were obtained from the Medical Research Council Integrated Epidemiology Unit (MRC-IEU). 47 Single nucleotide polymorphisms (SNPs) associated with RA were screened as instrumental variables (IV). The causal relationship between RA and pregnancy loss and IUGR were assessed by 5 MR methods, mainly inverse variance weighting (IVW). Sensitivity analyses were also performed to test the stability of the results. RESULTS: Bidirectional MR showed that genetically predicted RA was causally associated with pregnancy loss and IUGR in forward MR analyses, and that RA significantly increased pregnancy loss [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.00-1.33, P = .03] and IUGR (OR = 1.08, 95% CI: 1.01-1.15, P = .019). In the reverse MR, there was no causal association between pregnancy loss (P = .15) and IUGR (P = .87) and RA. CONCLUSION: This study found a significant genetic association between RA and pregnancy loss and IUGR. RA is considered to be a high-risk factor for adverse maternal outcomes. Pre-pregnancy prophylaxis and intra-pregnancy control of patients should be emphasized to reduce the incidence of adverse pregnancy outcomes such as pregnancy loss and IUGR.

Rate of deterioration of umbilical artery Doppler indices in fetuses with severe early-onset fetal growth restriction.

BACKGROUND: Incorporation of umbilical artery Doppler in the surveillance of fetal growth restriction has been shown to reduce the risk of perinatal deaths. Systole/Diastole ratio, Pulsatility Index and Resistance Index are obtained upon Doppler interrogation of the umbilical artery however it is unknown which index predicts more advanced stages of placental deterioration. OBJECTIVE: This study aimed to examine risk factors for the development of absent or reversed end-diastolic velocity and the time intervals of deterioration from normal umbilical artery end-diastolic velocity (indicated by systole/diastole ratio, pulsatility index, or resistance index) to decreased and absent or reversed end-diastolic velocity in fetuses with early-onset severe fetal growth restriction. STUDY DESIGN: This was a retrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight or abdominal circumference below the third percentile) and early-onset (diagnosed between 20 0/7 and 31 6/7 weeks of gestation) fetal growth restriction were included. Patients with fetal genetic or structural anomalies, suspected congenital infections, absent or reversed end-diastolic velocity at diagnosis, poor pregnancy dating, and absence of follow-up ultrasounds were excluded. Estimated fetal weight, abdominal circumference, and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for absent or reversed end-diastolic velocity, we performed backward stepwise logistic regression and calculated odds ratios with 95% confidence intervals. Kaplan-Meier curves were compared using log-rank tests. RESULTS: A total of 985 patients met the inclusion criteria, and 79 (8%) progressed to absent or reversed end-diastolic velocity. Factors associated with development of absent or reversed end-diastolic velocity included gestational age at diagnosis (adjusted odds ratio, 4.88 [95% confidence interval, 2.55-9.37] at 20 0/7 to 23 6/7 weeks; adjusted odds ratio, 1.56 [95% confidence interval, 0.86-2.82] at 24 0/7 to 27 6/7 weeks compared with 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (adjusted odds ratio, 2.37 [95% confidence interval, 1.33-4.23]). Rates of progression from diagnosis of fetal growth restriction with normal umbilical artery Doppler to absent or reversed end-diastolic velocity were significant after 4 weeks from diagnosis (5.84% [95% confidence interval, 4.50-7.57]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar at 1 and 2 weeks. However, the rate of progression from normal to abnormal systole/diastole ratio compared with the rates of progression from normal to abnormal pulsatility index or resistance index was higher at 4 and 6 weeks. Deterioration from abnormal indices to absent or reversed end-diastolic velocity was shorter with abnormal resistance index and pulsatility index when compared with the systole/diastole ratio at 2, 4, and 6 weeks after diagnosis and at 6 weeks, respectively. CONCLUSION: Earlier gestational age at diagnosis and chronic hypertension are considered as risk factors for Doppler deterioration and development of absent or reversed end-diastolic velocity in the umbilical artery. With normal Doppler indices, significant deterioration and progression to absent or reversed end-diastolic velocity is unlikely until 4 weeks after diagnosis. Abnormal systole/diastole ratio seems to appear first. However, abnormal pulsatility index or resistance index was associated with absent or reversed end-diastolic velocity.

The effect of possible mediators on the association between chewing khat during pregnancy and fetal growth and newborn size at birth in Eastern Ethiopia.

INTRODUCTION: Restriction in the growth of the fetus is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Documented existing scientific evidence have shown the effects of maternal drugs use, alcohol drinking, tobacco smoking, cocaine use and heroin use on fetal growth restriction. However, data is lacking on the effects of khat chewing during pregnancy on fetal growth status and newborn size at birth. Therefore, the aim of the present study was to measure the effect of chewing khat during pregnancy on fetal growth and size at birth in eastern Ethiopia. METHOD: A cohort study was conducted in selected health institutions in eastern Ethiopia. All pregnant women fulfilled the eligibility criteria in the selected health institutions was the source population. The calculated sample size of exposed and unexposed groups included in the study, in total, was 344. Data collection was performed prospectively by interviewers administered questionnaires, and anthropometric, clinical and ultrasound measurements. Data was analyzed using SPSS version 27 and STATA version 16 software. The survival analysis (cox proportional hazards model) and generalized linear model (GLM) for the binomial family analysis were performed to estimate the crude and adjusted relative risk and attributable risk (AR) with corresponding 95% CI of chewing khat on fetal growth restriction. The mediation effect has been examined through Generalized Structural Equation Modeling (GSEM) analysis using the Stata 'gsem' command. Statistically significant association was declared at p-value less than 5%. RESULTS: In the present study, the incidence of fetal growth restriction (FGR) among the study cohorts was 95 (29.7%); of this, 81 (85.3%) were among khat chewer cohorts. The relative risk of fetal growth restriction among khat chewer cohort mothers was significantly higher (aRR = 4.32; 95%CI 2.62-7.12). Moreover, the incidence of small for gestational age at birth among the present study cohorts was 100 (31.3%); 84 (84%) were from khat chewer cohorts' deliveries. More importantly, in the present study, 98.95% of the ultrasound-identified fetuses with FGR were found to be SGA at birth. Hence, in the current study, FGR was highly associated with SGA at birth. In additional analysis, the regression coefficient of khat chewing during pregnancy on fetal growth restriction has been decreased in size from path o, ß = 0.43, p < 0.001 to path o', ß = 0.32, p < 0.001, after adjusting for gestational hypertension and maternal anemia. CONCLUSION: In sum, the present study showed khat chewing during pregnancy is not simply affected the mothers, but it also affected the unborn fetuses. Therefore, the health workers as well as the local community and religious leaders should give high emphasis on provision of health education regarding the damage of chewing khat by pregnant mothers, with especial focus of the effects on their fetuses.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Practice variation in timing of antenatal corticosteroid administration in early-onset fetal growth restriction: A secondary analysis of the Dutch STRIDER study.

INTRODUCTION: In early-onset fetal growth restriction the fetus fails to thrive in utero due to unmet fetal metabolic demands. This condition is linked to perinatal mortality and severe neonatal morbidity. Maternal administration of corticosteroids in high-risk pregnancies for preterm birth at a gestational age between 24 and 34 weeks has been shown to reduce perinatal mortality and morbidity. Practice variation exists in the timing of the administration of corticosteroids based on umbilical artery monitoring findings in early-onset fetal growth restriction. The aim of this study was to examine differences in neonatal outcomes when comparing different corticosteroid timing strategies. MATERIAL AND METHODS: This was a post-hoc analysis of the Dutch STRIDER trial. We examined neonatal outcomes when comparing institutional strategies of early (umbilical artery pulsatility index >95th centile) and late (umbilical artery shows absent or reversed end-diastolic flow) administration of corticosteroids. The primary outcomes were neonatal mortality and a composite of neonatal mortality and neonatal morbidity, defined as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis or retinopathy of prematurity. We also analyzed predictors for adverse neonatal outcomes, including gestational age at delivery, birthweight, maternal hypertensive disorders, and time interval between corticosteroids and birth. RESULTS: A total of 120 patients matched our inclusion criteria. In 69 (57.5%) the early strategy was applied and in 51 (42.5%) patients the late strategy. Median gestational age at delivery was 28 4/7 (± 3, 3/7) weeks. Median birthweight was 708 (± 304) g. Composite primary outcome was found in 57 (47.5%) neonates. No significant differences were observed in the primary outcome between the two strategies (neonatal mortality adjusted odds ratio [OR] 1.22, 95% CI 0.44-3.38; composite primary outcome adjusted OR 1.05, 95% CI 0.42-2.64). Only gestational age at delivery was a significant predictor for improved neonatal outcome (adjusted OR 0.91, 95% CI 0.86-0.96). CONCLUSIONS: No significant differences in neonatal outcomes were observed when comparing early and late strategy of antenatal corticosteroid administration on neonatal outcomes in pregnancies complicated by early-onset fetal growth restriction. We found no apparent risk contribution of interval between corticosteroid administration and delivery in multivariate analysis. Gestational age at delivery was found to be an important predictor of neonatal outcome.

Outcome of monochorionic diamniotic twin pregnancy with selective intrauterine growth restriction, a single center study in China.

INTRODUCTION: This retrospective study aimed to evaluate clinical outcomes of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). MATERIALS AND METHODS: MCDA twins, either sIUGR and non-sIUGR, underwent expectant management from 2016 to 2019 in our hospital were included. sIUGR fetuses were classified into three types according to umbilical artery Doppler assessment. Non-sIUGR were considered as the control group. Outcomes were pregnancy outcomes and maternal complications. RESULTS: Forty-three sIUGR (type I: 23; type II: 14, and type III: 6) and 282 non-sIUGR fetuses were included. The sIUGR group had a significantly earlier birth, lower birth weight of the twins, larger inter-twin weight difference, lower Apgar score of the twins, and higher intrauterine fetal death (IUFD) than the non-sIUGR group (all p < 0.001). The same trend was found in the sIUGR type II group compared to type I and III groups. A significantly lower gestational diabetes rate (p = 0.01) and placenta weight (p < 0.001), and higher proportions of abnormal placental umbilical cord insertion (p < 0.001), and ultrasound Doppler monitoring indicators (p = 0.006) were found in the sIUGR group than the non-sIUGR group. CONCLUSIONS: The MCDA twins with sIUGR showed poorer outcomes than the non-sIUGR group. Doppler interrogation was a useful clinical marker for fetal outcome.

Patients with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes.

BACKGROUND: Increased rates of adverse pregnancy outcomes have been reported in association with rheumatologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis. However, little is known about pregnancy outcomes in patients with autoimmune skin diseases. OBJECTIVE: This study aimed to determine the frequency of adverse pregnancy outcomes in patients with autoimmune skin diseases. We hypothesized that similar to rheumatic diseases, the rate of adverse pregnancy outcomes in patients with autoimmune skin diseases would be higher than the general population. STUDY DESIGN: This is a case control study using the TriNetX US Collaborative Network, which is a database of electronic medical records of >95 million patients seen at 57 healthcare organizations in the United States. All pregnant women between the ages of 15 and 44 years who were seen at a healthcare organization between January 1, 2016 and December 31, 2021 were included. Participants with autoimmune skin disease were matched to healthy controls and controls with systemic rheumatologic conditions (systemic lupus erythematosus or rheumatoid arthritis). For both the autoimmune skin disease and healthy control groups, those with systemic rheumatologic condition or hidradenitis suppurativa were excluded. The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia or eclampsia, gestational diabetes mellitus, intrauterine growth restriction, preterm premature rupture of membranes, preterm birth, and stillbirth. Patients with autoimmune skin diseases and controls were 1:1 propensity score-matched by age, race, ethnicity, comorbidities, obesity, and substance use. For each outcome, odds ratio with a 95% confidence interval was calculated. RESULTS: A total of 2788 patients with autoimmune skin diseases were matched to 2788 healthy controls. Patients with autoimmune skin diseases were at a higher risk of spontaneous abortions than controls (odds ratio, 1.54; 95% confidence interval, 1.36-1.75; P<.001). Compared with patients with systemic lupus erythematosus, patients with autoimmune skin diseases were at lower risk of having infants with intrauterine growth restriction (odds ratio, 0.59; 95% confidence interval, 0.4-0.87; P=.01), preterm birth (odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P=.04), and stillbirth (odds ratio, 0.50; 95% confidence interval, 0.25-0.97; P=.04). The differences in adverse pregnancy outcomes between patients with autoimmune skin diseases and those with rheumatoid arthritis were not statistically significant. CONCLUSION: Patients with autoimmune skin diseases are at a higher risk of spontaneous abortions than patients without autoimmune skin diseases. When analyzed by each autoimmune skin disease, patients with cutaneous lupus erythematosus or vitiligo remained at increased risk of spontaneous abortions compared with patients without autoimmune skin diseases. Patients with autoimmune skin diseases have similar risks of adverse pregnancy outcomes as patients with rheumatoid arthritis, but lower risks than patients with systemic lupus erythematosus.

Predictive ability of fetal growth charts in identifying kindergarten-age developmental challenges: a cohort study.

BACKGROUND: The Society for Maternal-Fetal Medicine recommends defining fetal growth restriction as an estimated fetal weight or abdominal circumference <10th percentile of a population-based reference. However, because multiple references are available, an understanding of their ability to identify infants at increased risk due to fetal growth restriction is critical. Previous studies have focused on the ability of different population references to identify short-term outcomes, but fetal growth restriction also has longer-term consequences for child development. OBJECTIVE: This study aimed to estimate the association between estimated fetal weight percentiles on the INTERGROWTH-21st and World Health Organization fetal growth charts and kindergarten-age childhood development, and establish the charts' discriminatory ability in predicting kindergarten-age developmental challenges. STUDY DESIGN: We conducted a retrospective cohort study linking obstetrical ultrasound scans conducted at BC Women's Hospital, Vancouver, Canada, with population-based standardized kindergarten test results. The cohort was limited to nonanomalous, singleton fetuses scanned at ≥28 weeks' gestation from 2000 to 2011, with follow-up until 2017. We classified estimated fetal weight into percentiles using the INTERGROWTH-21st and World Health Organization charts. We used generalized additive modeling to link estimated fetal weight percentile with routine province-wide kindergarten readiness test results. We calculated the area under the receiver-operating characteristic curve and other measures of diagnostic accuracy with 95% confidence intervals at select percentile cut-points of the charts. We repeated analyses using the Hadlock chart to help contextualize findings. The main outcome measure was the total Early Development Instrument score (/50). Secondary outcomes were Early Development Instrument subdomain scores for language and cognitive development, and for communication skills and general knowledge, as well as designation of "developmentally vulnerable" or "special needs". RESULTS: Among 3418 eligible fetuses, those with lower estimated fetal weight percentiles had systematically lower Early Development Instrument scores and increased risks of developmental vulnerability. However, the clinical significance of differences was modest in magnitude (eg, total Early Development Instrument score -2.8 [95% confidence interval, -5.1 to -0.5] in children with an estimated fetal weight in 3rd-9th percentile of INTERGROWTH-21st chart [vs reference of 31st-90th]). The charts' predictive abilities for adverse child development were limited (eg, area under the receiver-operating characteristic curve <0.53 for all 3 charts). CONCLUSION: Lower estimated fetal weight percentiles on the INTERGROWTH-21st and World Health Organization charts indicate increased risks of adverse kindergarten-age child development at the population level, but are not accurate individual-level predictors of adverse child development.

Importance of antenatal identification of small for gestational age fetuses on perinatal and childhood outcomes: A register-based cohort study.

INTRODUCTION: Fetal growth restriction (FGR) is associated with increased risk for stillbirth, perinatal morbidity, cerebral palsy, neurodevelopmental disorders and cardiovascular disease later in life. Identifying small-for-gestational-age (SGA) fetuses is crucial for the diagnosis of FGR. The aim of this study was to investigate the association between antenatal identification of SGA fetuses and severe adverse perinatal and childhood outcome. MATERIAL AND METHODS: A register-based cohort study of all newborns delivered in Stockholm in 2014 and 2017. INCLUSION CRITERIA: singleton pregnancies without chromosomal aberrations or structural abnormalities, with a gestational age at delivery between 22+0 and 43+0 (n = 48 843). Data from childbirth records were linked to data from nationwide Swedish registers. Pregnancy including offspring data were reviewed. Adverse outcomes for non-identified and identified SGA newborns were compared using logistic regression models. Primary outcome was a composite outcome called severe adverse outcome, defined as at least one of the following: stillbirth, severe newborn distress (Apgar score <4 at 5 min, pH <7 or resuscitation activities >10 min), severe neonatal outcome (hypoxic ischemic encephalopathy 2-3, necrotizing enterocolitis, neonatal seizures, intraventricular hemorrhage grade 3-4, bronchopulmonary disease or death at <1 year), severe childhood outcome (cognitive impairment or motor impairment or cerebral palsy or hearing impairment or visual impairment or death at 1-3 years old). Secondary outcomes were stillbirth, severe newborn distress, severe neonatal outcome, severe childhood outcome. RESULTS: No association was found between antenatal identification of SGA fetuses and severe adverse outcome using the complete composite outcome (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.93-1.53). In subgroup analyses, non-identified SGA fetuses had an almost fivefold increased risk for stillbirth (aOR 4.79, 95% CI 2.63-8.72) and an increased risk for severe newborn distress (aOR 1.36, 95% CI 1.02-1.82), but a decreased risk for severe childhood outcome (aOR 0.63, 95% CI 0.40-0.99). No association was found between antenatal identification of SGA and severe neonatal outcome. CONCLUSIONS: Non-identified SGA fetuses have an increased risk for stillbirth and severe newborn distress. Conversely, identified SGA fetuses have an increased risk for severe childhood outcome.

Impact of Sjögren's syndrome on maternal and fetal outcomes following pregnancy: a systematic review and meta-analysis of studies published between years 2007-2022.

OBJECTIVE: To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy. METHODS: We performed a literature search based on PubMed, Web of science, Wan fang, China National Knowledge Infrastructure and ProQuest databases from 1 January 2007 to 6 November 2022. Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of the evidence. Systematic reviews and meta-analyses were performed using RevMan 5.3 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Trial sequential analyses were performed by TSA 0.9. RESULTS: Nine studies with 2341 patients and 2472 pregnancies with SS were included in our analysis. This current analysis showed pregnancy hypertension and preeclampsia/eclampsia to be significantly higher in pregnant women with SS compared to pregnant women without SS (OR: 1.65, 95% CI: 1.04-2.63; P = 0.03), (OR: 2.06, 95% CI: 1.16-3.65; P = 0.01) respectively. Cesarean section, thromboembolic disease, premature rupture of membranes, and spontaneous abortion were also significantly higher in the SS women with OR: 2.07, 95% CI: 1.48-2.88; P < 0.0001, OR: 9.45, 95% CI: 1.99-44.87; P = 0.005, OR: 1.36, 95% CI: 1.13-1.64; P = 0.001, OR: 9.30, 95% CI: 4.13-20.93; P < 0.00001, respectively. Significantly higher premature births were observed with infants who were born from SS mothers (OR: 2.19, 95% CI: 1.54-3.12; P < 0.0001). Infants defined as 'small for gestational age/intrauterine growth restriction' and 'weighing < 2500 g' were also significantly higher in patients suffering from SS (OR: 2.26, 95% CI: 1.38-3.70; P = 0.001), (OR: 3.84, 95% CI: 1.39-10.61; P = 0.009) respectively. In addition, live birth significantly favored infants who were born from mothers without SS (OR: 21.53, 95% CI: 8.36-55.44; P < 0.00001). Subgroup analysis by sample size revealed that pregnancy hypertension risk has significantly increased in small cohort (OR: 2.74, 95%CI: 1.45-5.18), and a slight increase was found in population-based studies (OR: 1.14, 95%CI: 0.91-1.43). In both small cohorts and population-based researches, cesarean section was significantly higher in SS (OR: 2.13, 95% CI: 1.29, 3.52; OR: 1.85, 95% CI: 1.29-2.64, respectively). The number of infants with intrauterine growth restriction did not grow in the population-based researches (OR: 2.07, 95%CI: 0.92-4.66) although there has been an increase in small reports (OR: 2.53, 95%CI: 1.16-5.51). Subgroup analysis was conducted on the basis of study location (not Asian vs. Asian countries) indicated that cesarean section was significantly higher in SS in both countries (OR: 1.69, 95% CI: 1.31-2.18; OR: 3.37, 95% CI: 2.39-4.77, respectively). CONCLUSION: This meta-analysis has shown SS to have a high impact on maternal and fetal outcomes following pregnancy.

Associations between placental pathology and poor intrauterine growth among a cohort of mother-infant singleton pairs in Leyte, the Philippines.

OBJECTIVE: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth. METHODS: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors. RESULTS: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004). CONCLUSION: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities.

Selective fetal growth restriction in dichorionic diamniotic twin pregnancy: systematic review and meta-analysis of pregnancy and perinatal outcomes.

OBJECTIVE: Most of the published literature on selective fetal growth restriction (sFGR) has focused on monochorionic twin pregnancies. The aim of this systematic review was to report on the outcome of dichorionic diamniotic (DCDA) twin pregnancies complicated by sFGR. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched. The inclusion criteria were DCDA twin pregnancies complicated by sFGR. The outcomes explored were intrauterine death (IUD), neonatal death and perinatal death (PND), survival of at least one and both twins, preterm birth (PTB) (either spontaneous or iatrogenic) prior to 37, 34, 32 and 28 weeks' gestation, pre-eclampsia (PE) or gestational hypertension, neurological, respiratory and infectious morbidity, Apgar score < 7 at 5 min, necrotizing enterocolitis, retinopathy of prematurity and admission to the neonatal intensive care unit (NICU). A composite outcome of neonatal morbidity, defined as the occurrence of respiratory, neurological or infectious morbidity, was also evaluated. Random-effects meta-analysis was used to analyze the data, and results are reported as pooled proportion or odds ratio (OR) with 95% CI. RESULTS: Thirteen studies reporting on 1339 pregnancies with sFGR and 6316 pregnancies without sFGR were included. IUD occurred in 2.6% (95% CI, 1.1-4.7%) of fetuses from DCDA pregnancies with sFGR and 0.6% (95% CI, 0.3-9.7%) of those from DCDA pregnancies without sFGR, while the respective values for PND were 5.2% (95% CI, 3.5-7.3%) and 1.7% (95% CI, 0.1-5.7%). Spontaneous or iatrogenic PTB before 37 weeks complicated 84.1% (95% CI, 55.6-99.2%) of pregnancies with sFGR and 69.1% (95% CI, 45.4-88.4%) of those without sFGR. The respective values for PTB before 34, 32 and 28 weeks were 18.4% (95% CI, 4.4-38.9%), 13.0% (95% CI, 9.5-17.1%) and 1.5% (95% CI, 0.6-2.3%) in pregnancies with sFGR and 10.2% (95% CI, 3.1-20.7%), 7.8% (95% CI, 6.8-9.0%) and 1.8% (95% CI, 1.3-2.4%) in those without sFGR. PE or gestational hypertension complicated 19.9% (95% CI, 12.4-28.6%) of pregnancies with sFGR and 12.8% (95% CI, 10.4-15.4%) of those without sFGR. Composite morbidity occurred in 28.2% (95% CI, 7.8-55.1%) of fetuses from pregnancies with sFGR and 13.9% (95% CI, 6.5-23.5%) of those from pregnancies without sFGR. When stratified according to the sFGR status within a twin pair, composite morbidity occurred in 39.0% (95% CI, 11.1-71.5%) of growth-restricted fetuses and 29.9% (95% CI, 3.5-65.0%) of appropriately grown fetuses (OR, 1.9 (95% CI, 1.7-3.1)), while the respective values for PND were 3.0% (95% CI, 1.8-4.5%) and 1.6% (95% CI, 0.9-2.6%) (OR, 2.1 (95% CI, 1.0-4.1)). On risk analysis, DCDA pregnancies complicated by sFGR had a significantly higher risk of IUD (OR, 5.2 (95% CI, 3.2-8.6)) and composite morbidity or admission to the NICU (OR, 3.2 (95% CI, 1.9-5.6)) compared to those without sFGR, while there was no difference in the risk of PTB before 34 weeks (P = 0.220) or PE/gestational hypertension (P = 0.210). CONCLUSIONS: DCDA twin pregnancies complicated by sFGR are at high risk of perinatal morbidity and mortality. The findings of this systematic review are relevant for counseling and management of complicated DCDA twin pregnancies, in which twin-specific, rather than singleton, outcome data should be used. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association between graded subchorionic hematoma and adverse pregnancy outcomes in singleton pregnancies: a prospective observational cohort study.

OBJECTIVE: To investigate whether different grades of subchorionic hematoma (SCH) are involved in the timing of birth and the development of adverse pregnancy outcomes in singleton pregnant women. METHODS: A total of 171 women with singleton pregnancies, 72 of whom had SCH before 20 weeks and between 12 and 20 weeks of gestational age (GA), were included in this study conducted between January 2018 and December 2021. These patients were divided into three subgroups based on the size of the subchorionic hematoma on ultrasound imaging. Baseline demographic data, obstetric outcomes, and risk factors for subchorionic hematoma were compared for the two groups. RESULTS: A higher number of pregnancies from the SCH group resulted in miscarriage (30.56% versus 2.02%, p < 0.0001), early preterm birth (8.33% versus 1.01%, p = 0.0035), premature rupture of membranes (15.28% versus 4.04%, p = 0.0103), fetal growth restriction (9.72% versus 0%, p = 0.0015), and delivery 13.18 days earlier (274.34 ± 11.25 versus 261.16 ± 29.80, p = 0.0013) than those from the control group. Compared with SCH detected before 12 weeks of GA, the rate of miscarriage increased, and the live birth rate decreased significantly in patients with SCH caught between 12 and 20 weeks of GA. With the increase in hematoma size, the likelihood of miscarriage increased significantly. Further analysis found that delivery occurred earlier in the medium/large SCH group (271.49 ± 23.61 versus 253.28 ± 40.68/261.77 ± 22.11, p = 0.0004/0.0073) but not in the small SCH group (274.34 ± 11.25 versus 267.85 ± 21.01, p = 0.2681) compared to the control group. Our results also showed that the anterior placenta (52.04% versus 33.33%, p = 0.0005, OR = 0.3137, 95% CI [0.1585, 0.601]) is a protective factor for subchorionic hematoma. CONCLUSION: Our study shows that women with SCH are at a higher risk of adverse pregnancy outcomes and are independently associated with miscarriage, early preterm birth, premature rupture of membranes, and fetal growth restriction. A subchorionic hematoma, especially detected between 12 and 20 weeks of GA, is very likely to cause miscarriage or preterm birth in women with a medium or large subchorionic hematoma.