Hemoglobin concentration in multiple versus singleton pregnancies — retrospective evidence for physiology not pathology

Continuous quality improvement and assisted reproductive technology multiple gestations: some progress, some answers, more questions

Neonatal outcomes of antenatal corticosteroids in preterm multiple pregnancies compared to singletons.

The aim: To carry out a comparative statistical analysis of obstetric and perinatal complications in singleton and multiple pregnancies once assisted reproductive technologies (ART) are applied according to the records taken from archival materials (maternity and delivery records) and identify the clinical features of multiple pregnancy. Materials and methods: Over the period of 2017-2019, 522 women gave birth in LELEKA Maternity Hospital LLC after using assisted reproductive technologies and 331 women among them were followed-up in the women's health center of LELEKA maternity hospital. Among these women (522) with singleton pregnancy 445 women gave birth, while in multiple pregnancy - 77. The statistical analysis of 150 maternity and delivery records was carried out. All pregnant women were divided into two groups: group 1 - 75 women having singleton pregnancy after ART; group 2 - 75 women having multiple pregnancy after ART. Women getting pregnant after ART, or in vitro fertilization (IVF) and five-day frozen embryo transfer to be exact, turned out to be the selection criterion for a comparative statistical analysis. Mathematical methods for research were used as O.P. Mintser (2013) suggested. The reliability of the digit cancellation test was calculated using the Fisher's exact test and Student's T-test. Graphs were designed using Microsoft Excel. Results: The complications of early multiple pregnancy were the following: anemia (47.8% as opposed to 22.9%, p<0.01), placental insufficiency (43.3% in contrast to 22.9%, p<0.01), threatened abortion (41.8% in contrast to 28.6%, p<0.01). The complications in late pregnancy are as follows: preeclampsia (52.7% as opposed to 20.6%, p <0.01), intrauterine growth restriction (20.0% as opposed to 7.4%, p <0.01), anemia in pregnancy (76.4% in contrast to 32.4%, p<0.01), placental insufficiency (47.3% in contrast to 22.1%, p<0.05). Conclusions: Multiple pregnancy is a high risk for anemia in pregnancy, preeclampsia, placental insufficiency, early intrauterine growth restriction and fetal distress in pregnancy and labor. It predetermines the high level of a caesarean section. Therefore, further research aimed at prediction and prevention of obstetric and perinatal complications in multiple pregnancy after ART is currently topical.

IntroductionChorangiomas (CAs) are the most common non-trophoblastic tumor-like-lesions of the placenta. Although the clinical significance of small CAs is unknown, the large lesions are often associated with maternal and fetal complications. The aim of our study was to assess the maternal clinical characteristics and neonatal outcome in singleton and multiple pregnancies with placental CA.Materials and MethodsAmong 15742 selected placentas 170 CAs were diagnosed. Pregnancy and neonatal outcomes were analyzed in singleton (n = 121) and multiple (n = 49) pregnancy groups including 121 and 100 neonates, respectively.ResultsThe frequency of APGAR score <7 at 5 minutes (p = 0,012), abnormal pulsatility index (p = 0,034), and abnormal blood flow class (p = 0,011) were significantly higher in neonates from singleton compared to multiple pregnancies. Significantly smaller CAs in singleton pregnancies were related to small for gestational age neonates (p = 0,00040) and neonates admitted to the neonatal care unit (p = 0,028). In singleton pregnancies, significantly smaller CAs were associated to maternal preeclampsia (p = 0,039) and larger CAs to multiparity (p = 0,005) and smoking (p = 0,001) groups. The frequency of preeclampsia was high in both singleton and multiple pregnancy groups (41,32% vs 26,53%, respectively), however, the difference did not reach the level of statistical significance.DiscussionA high incidence of preeclampsia in cohort of placental CA might lead to a possible recognition of CAs as potential morphologic indicator of placental hypoxia.ConclusionA more favorable pregnancy outcome in multiple gestations compared to the singleton gestations with CAs might reflect an adaptive mechanism for increased demand of oxygen and associated placental tissue hypoxia in this group.

During the past 20 years, the prevalence of Down syndrome (DS) has increased with the increase in mean maternal age. The prevalence of multiple births has also increased because of older maternal age and use of assisted reproductive technologies. This study was designed to determine the maternal age–specific prevalence of DS in monozygotic and dizygotic pregnancies, assess risk relative to singleton pregnancies, as well as compare prenatal diagnosis and pregnancy outcomes for DS fetuses in multiple and singleton pregnancies. The database of the European Surveillance of Congenital Anomalies includes live-born congenital anomaly cases, stillborn cases and fetal deaths after 20 weeks’ gestation, as well as prenatally diagnosed cases resulting in termination of pregnancy for fetal anomaly. The study population consisted of 14,827,105 pregnancies between 1990 and 2009, of which 2.89% were multiple gestations. Individual fetuses/babies with DS from multiple and singleton pregnancies were considered “cases.” Twin pairs with both twins having DS were “concordant” pairs. Relative risk (RR) with the 95% confidence interval (CI) was used to estimate the prevalence of cases with DS among multiple births relative to that among singleton births. From 1990 to 1999, the total corrected prevalence of DS cases from multiple pregnancies as opposed to singleton pregnancies per 10,000 births was 0.40 (95% CI, 0.36–0.45), rising to 0.47 (95% CI, 0.42–0.53) in 2000 to 2009 (P > 0.05). Overall (1990–2009), the prevalence of DS cases per 10,000 multiple births was 15.1 (95% CI, 14.6–15.9); and per 10,000 singleton births, 20.1 (95% CI, 19.9–20.3). The prevalence of DS cases per 10,000 multiple births rose with age of 44 years or younger, after which it was considerably lower. The adjusted RR of DS for babies from multiple births relative to singleton births was 0.58 (95% CI, 0.53–0.62). Of 19,397 babies born to mothers older than 44 years, 2043 (10.5%) were from multiple births. Only 1 fetus from a multiple pregnancy was a DS case, a prevalence of 4.48 (95% CI, 0.67–35.1) per 10,000 multiple births, compared with 562 singleton DS cases, a prevalence of 327 (95% CI, 301–356) per 10,000 singleton births (RR, 0.015; 95% CI, 0.002–0.107). In 8.7% (n = 54) of affected pairs, the twins were concordant for DS, 51 same-sex twin pairs and 3 unlike-sex twin pairs. The maternal age–adjusted RR of a monozygotic pregnancy being affected was 0.34 (95% CI, 0.25–0.44) compared with singleton pregnancies. No affected monozygotic twin pregnancies occurred in the group older than 44 years. For dizygotic pregnancies, the maternal age–adjusted RR of at least 1 twin being affected was 1.34 (95% CI, 1.23–1.46) compared with singleton pregnancies. For age older than 44 years, the RR was 0.04 (95% CI, 0.01–0.27). The proportion of DS cases prenatally diagnosed was lower for multiple than for singleton pregnancies at all maternal ages, for an overall maternal age–adjusted odds ratio (OR) of 0.62 (95% CI, 0.50–0.78). The overall proportion of termination of pregnancy for fetal anomaly cases from multiple pregnancies was lower than singletons at every maternal age, giving an overall maternal age–adjusted OR of 0.52 (95% CI, 0.41–0.65). Down syndrome cases from multiple births were not more likely to be stillbirths/fetal deaths than from singleton births; the maternal age–adjusted OR was 1.03 (95% CI, 0.59–1.78). Individual fetuses from twin pregnancies are at lower risk for DS than those from singleton pregnancies. The estimates of the lower maternal age–specific DS risk in twin pregnancies, combined with the clinician’s knowledge of zygosity/chorionicity and maternal age at ovulation for women having assisted reproductive technologies, should allow more accurate risk estimates for genetic counseling and prenatal screening.

To analyze the clinical differences between multiple and singleton pregnancies with early-onset pre-eclampsia. The present retrospective cohort study included patients with early-onset pre-eclampsia diagnosed at a tertiary hospital in China between January 2012 and June 2014. The patients were divided into a multiple pregnancy group (MP group) and a singleton pregnancy group (SP group). Differences in maternal and fetal outcomes before and after birth were compared between the two groups. Overall, 100 patients were included (21 MP group; 79 SP group). The systolic and diastolic blood pressure values at admission were significantly lower in the MP group than in the SP group (P=0.032 and P=0.015, respectively), and the incidence of pregnancy edema was significantly higher (P=0.015). Moreover, the mean neonatal birth weight in the MP group was significantly higher than that in the SP group (P<0.001). The frequencies of abnormal umbilical arterial resistance score, abnormal fetal heart rate, low birth weight, low Apgar score, neonatal cardiovascular abnormalities, and neonatal infections were significantly lower in multiple pregnancies (P<0.05 for all). Early-onset pre-eclampsia in multiple pregnancies seems to have a protective effect on neonatal survival and improves maternal and fetal outcomes. Disease progression might be delayed when compared with early-onset pre-eclampsia in singleton pregnancies.

Congenital cytomegalovirus (cCMV) infection is an important cause of hearing loss and neurodevelopment delay. While data on vertical transmission and neonatal outcome after singleton pregnancy with cCMV are well established, only scarce reports have addressed cCMV in multiple birth pregnancies. Furthermore, no studies have yet compared the outcome after birth and long-term follow-up of children with cCMV born after a singleton versus multiple pregnancies. Infant outcome after birth of symptomatic versus asymptomatic infection was compared for infants born with cCMV after multiple (study group) and singleton (control group) pregnancies in a 1:2 ratio. Of 508 infants diagnosed with cCMV, 25 (4.9%) were born after a multiple pregnancy. Children in the study and control groups did not differ in terms of specific prenatal CMV investigations including amniocentesis and brain magnetic resonance imaging studies. However, prematurity rates were significantly higher in the study compared with control group (52% vs. 4%, P < 0.001). There was a higher rate of symptomatic cCMV infection in the study group than in the controls (48% vs. 14%, P < 0.001). Hearing impairment at birth was also more frequent in the study group (32% vs. 8%, P = 0.016). A long-term follow-up demonstrated that children in the study group had higher rates of neurologic sequelae (hearing impairment or neurodevelopmental delay) compared with children in the control group (20% vs. 4%, P = 0.016). Infants with cCMV born after multiple birth pregnancies are born earlier and have a higher risk of symptomatic disease at birth and worse long-term neurologic outcome than those born after a singleton pregnancy. This important group of children warrants meticulous prenatal and postnatal care.

In recent years there has been an increase in the frequency of multiple pregnancies and the associated perinatal losses. It is a result of multiple pregnancy in ART refers to a high-risk gestation, at which premature births occur in 2 times more often than in singleton pregnancies. The objective: to determine the role of pro-inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy, as a result of assisted reproductive technology. Patients and methods. to determine the pro-inflammatory cytokines that all pregnant with bagtopliddyam held immunosorbent assay, defined concentrations of interleukin (IL) in serum and cervical mucus. Results. The analysis of the levels of pro-inflammatory cytokines (IL-1, IL-8) in the test environment, found high concentrations in the surveyed women with multiple pregnancy, due to the use of ART, compared with spontaneous multiple and singleton pregnancy. Increased concentration of proinflammatory cytokines in patients with multiple pregnancy by ART is associated with their synthesis at the system level, it stimulated foci of inflammation in the female genitals and extragenital localization. This correlates with the clinical data and statistical analysis, patients with multiple pregnancy as a result of ART had weighed infectious-inflammatory history. Conclusion. The study showed that elevated levels of proinflammatory cytokines in the systemic and local level in patients with multiple pregnancy due to ART, typical for women with miscarriage, because of the physiological course of pregnancy characterized by the predominance of anti-inflammatory cytokines that prevent rejection of the fetus as a foreign factor. Based on the data obtained proved the role of systemic inflammatory factors in the genesis of preterm labor in women with a multiple pregnancy, as a result of assisted reproductive technology. Key words: multiple pregnancy, assisted reproductive technology, premature birth, interleukine-1, interleukine-8.

Background COVID-19 vaccines in pregnancy protect both pregnant individuals and young infants from severe illness via transplacental transfer of maternally-derived IgG. However, the impact of multiple (e.g. twin) pregnancy on transplacental transfer of SARS-CoV-2 IgG is unknown. We aimed to evaluate anti-Spike (S) antibody transfer among infants from twin pregnancies compared to singleton pregnancies. Methods We conducted a prospective cohort study among individuals with twin and singleton pregnancies who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery. We tested paired maternal and cord samples for anti-S IgG and used linear regression to evaluate associations between multiple or singleton pregnancy and anti-S antibody. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age (&amp;lt; 10th percentile) birthweight. Results We tested maternal/cord anti-S IgG from 25 twin and 291 singleton pregnancies. The median gestational age at delivery was 36 weeks for twin infants compared to 39 weeks for singleton infants. Median maternal anti-S IgG was 5812 BAU/mL (IQR:754, 16061) and 2971 BAU/mL (IQR:706, 14000) for twin and singleton pregnancies, respectively. Median cord anti-S IgG was 4110 BAU/mL (IQR: 527, 15937) and 3636 BAU/mL (IQR: 1019, 15465) for twin and singleton infants, respectively (Figure 1). Cord:maternal IgG ratios were significantly lower in twin pregnancies compared to singleton pregnancies (p &amp;lt; 0.01; Figure 2). After adjustment for covariates, there was no difference between maternal anti-S IgG concentrations (beta: -0.54; 95% confidence interval [CI]: -1.26,0.18; p=0.14), cord anti-S IgG concentrations (beta: -0.77; 95% CI: -1.68,0.13; p=0.10) or cord:maternal IgG ratios (beta: -0.07; 95% CI: -0.32,0.19; p=0.61) between twin and singleton pregnancies. Conclusion Twin and singleton infants benefit similarly from maternal COVID-19 vaccine during pregnancy. Higher risk pregnancies including multiple pregnancies should be considered in health policy discussions regarding COVID-19 vaccine timing in pregnancy. Disclosures Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

The objective: conduct a comparative clinical and statistical analysis of obstetric and perinatal complications in singleton and multiple pregnancies after assisted reproductive technologies (ART) according to archival documents (pregnancy observation data and birth history) and identify features of multiple pregnancy. Materials and methods. During the period 2017–2019, 522 women gave birth in maternity hospital «Leleka» after assisted reproductive technologies, 331 women were observed in the maternity hospital «Leleka». 445 women gave birth with a singleton pregnancy and 77 with a multiple pregnancy. A clinical and statistical analysis of 150 pregnancy and childbirth histories was performed. All pregnant women were divided into two groups: Group I – 75 pregnant women with singleton pregnancies after ART; Group II – 75 pregnant women with multiple pregnancies after ART. The selection criteria for comparative clinical and statistical analysis were women whose pregnancies occurred as a result of ART, namely by in vitro fertilization (IVF) using five-day frozen embryos. Mathematical research methods were performed in accordance with the recommendations of O.P. Minzer (2013). The reliability of the cancellation of the mean pairs was calculated using the Student’s and Fisher’s criteria. Graphs were designed using the program «Microsoft Excel». Results. Complications of early pregnancy in multiple pregnancies were: anemia (47.8% vs. 22.9%; p&lt;0.01), placental dysfunction (43.3% vs. 22.9%; p&lt;0.01), the threat of abortion (41.8% vs. 28.6%; p&lt;0.01). Complications of the second half of pregnancy: preeclampsia (52.7% vs. 20.6%; p&lt;0.01), fetal growth retardation (20.0% vs. 7.4%; p&lt;0.01), gestational anemia (76,4% vs. 32.4%; p&lt;0.01), placental dysfunction (47.3% vs. 22.1%; p&lt;0.05). Complications in childbirth in women with multiple pregnancies were as follows: premature rupture of membranes (30.9% vs. 10.3%; p&lt;0.05), anomalies of labor activity (16.4% vs. 5.9%; p&gt;0.05), fetal distress (29.1% vs. 14.7%; p&lt;0.05), premature placental abruption (3.6% vs. the absence of this indicator in group I). In patients of group II with multiple pregnancies 3.7 times more often the pregnancy ended prematurely compared with singleton (21.8% vs. 5.9%; p&lt;0.05). Early preterm births predominated, of which births occurred in 3.6% of cases at 22–28 weeks, 7.3% at 28–32 weeks, and 6.4% at 32–34 weeks. Significant increase in the frequency of 32.7% of abdominal births in multiple pregnancies against 11.8% of patients in pregnancy with a single fetus (p&lt;0.01). The structure of indications in patients of group II was as follows: severe preeclampsia 27.8%, development of fetal growth retardation and fetal distress of 11.1%, respectively, premature placental abruption 16.7%, the following single indications (pelvic presentation of the fetus, transverse or oblique position of the fetus, clinically narrow pelvis, abnormalities of labor, scar on the uterus) – 33.3%. Significant increase in the total frequency of neonatal asphyxia of varying severity in multiple pregnancies (35.0% vs. 5.9%; p&lt;0.05), fetal growth retardation (27.3% vs. 11.8%; p&lt;0.01). Conclusions. Multiple pregnancies are a high risk factor for gestational anemia, preeclampsia, placental dysfunction, early fetal growth retardation, and fetal distress during pregnancy and childbirth. This causes a high level of abdominal delivery. Therefore, further research to predict and prevent obstetric and perinatal complications in multiple pregnancies after ART is relevant today. Keywords: obstetric and perinatal complications of pregnancy, multiple pregnancy, assisted reproductive technologies.

Maternal and neonatal outcomes in multiple pregnancy: A multicentre study in the Beijing population

Thirty-five multiple and 168 singleton fetal weight estimations were made in an Australian population using the tables of Warsof et al., which have been computed from a North American population. The estimated fetal weights were compared to the actual birth weights within 96 h of estimation. Correlation coefficients of the actual birth weight with the estimated fetal weight for the total group, singleton and multiple pregnancies respectively, were 0.967, 0.969 and 0.933. The percentages of estimated fetal weights falling within 10% of the actual birth weight were for the three groups, 79.3%, 77.9% and 85.7% respectively. Individual weight sub-groups, less than 1500 g, 1500-2500 g, 2500-4000 g and greater than 4000 g, showed correlation coefficients of 0.84, 0.838, 0.839 and 0.759 respectively, which compare favourably to published studies of North American populations using this method. It is concluded that ultrasonic fetal weight estimation using the North American computerized tables of Warsof et al. is appropriate for an Australian population and is valid for both singleton and multiple pregnancies.

Introduction. In assisted reproductive technology pregnancy (ARTP), the most unfavorable factor affecting perinatal outcomes is iatrogenic multiple gestation. Active introduction into practice of techniques that reduce the risk of multiple pregnancy, on the one hand, and management of ARTP in specialized medical centers with experience in working with this category of patients, on the other, can improve perinatal outcomes. Aim. Analysis of perinatal outcomes in assisted singleton and multiple pregnancies in order to assess the contribution of the multiple gestation factor to adverse health outcomes for newborns, and its relevance for improving of assisted reproductive technology. Materials and methods. A retrospective study of the ante-, intra- and early neonatal period was carried out in 672 infants born at the Medical Center AVICENNA (Novosibirsk) for the period from 2006 to 2015. The total sample was divided into 3 groups: 1st – infants from singleton ARTP (n = 345); 2nd – infants from multiple ARTP (n = 177); 3rd – infants from singleton spontaneous pregnancy (SSP) (n = 150) without infertility in the parental history, gravidity and parity were equal. A clinical and anamnestic method was used, with an assessment of the main parameters of the health status of infants and parents. Results. It was revealed that complications such as threatened miscarriage and preterm labor, cervical insufficiency, preeclampsia, and placental disorders are diagnosed significantly more often in multiple ARTP (p &lt; 0.001) compared with singleton ARTP. At the same time, in the setting of a specialized center, the majority of infants from ARTP were full-term, both in singleton (94.5% of cases) and in multiple (52.5% of cases) pregnancies. Any assisted reproductive technology pregnancy belongs to the group of high obstetric risk, but timely correction of complications significantly improves perinatal outcomes. Conclusion. ARTP belongs to the group of high obstetric risk, which increases significantly with multiple gestation. Management of an infertile couple in a specialized center with continuity at all stages from the moment of contacting the clinic to the birth of a child allows, despite the development of complications, to ensure the birth of full-term infants (both in singleton and multiple pregnancies), and in singleton pregnancies it leads to the birth of children, in main health indicators similar to those from a spontaneous pregnancy.

Prolonged intravenous ritodrine therapy: a comparison between multiple and singleton pregnancies

Controversy persists over whether preimplantation genetic testing (PGT) increases adverse maternal and neonatal outcomes. To quantify the risk of maternal and neonatal outcomes for singleton and multiple pregnancies conceived after PGT versus those conceived after IVF/ICSI. PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched from January 1990 to May 2025. Randomised controlled trials (RCTs) and observational studies separately reporting outcomes in singleton and multiple pregnancies. Random-effects models were used for calculating relative risks (RRs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs). Forty-two studies (43 663 PGT cases and 217 002 IVF/ICSI cases) were included for further analysis. The risks of very low birth weight (VLBW) (RR 0.66; 95% CI 0.58, 0.76), preterm birth (PTB) < 34 weeks (RR 0.79; 95% CI 0.73, 0.86), PTB < 32 weeks (RR 0.68; 95% CI 0.52, 0.89), and PTB < 28 weeks (RR 0.59; 95% CI 0.35, 0.99) in PGT singleton pregnancies were significantly lower than those in IVF/ICSI singleton pregnancies, and the risk of PTB < 32 weeks (RR 0.62; 95% CI 0.45, 0.86) in PGT multiple pregnancies was notably reduced compared to that in IVF/ICSI multiple pregnancies. The two groups showed comparable maternal outcome risks in singleton and multiple pregnancies. Nonetheless, no decisive conclusions can be drawn due to the low quality of evidence and challenges of statistical hypothesis testing. Additional high-quality RCTs with larger sample sizes and stringent methodologies are warranted to validate these findings.