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

Background: The global rise in pregnancies following assisted reproductive technology (ART) use has prompted ongoing evaluations into the impact of this technology on maternal and neonatal outcomes. Thus, this study aimed to compare outcomes between ART-conceived pregnancies and spontaneously conceived pregnancies, stratified by singleton and multiple pregnancies. Methods: We conducted a single-center retrospective cohort study at Gyeongsang National University Changwon Hospital in South Korea, using the medical records of women who delivered between January 2023 and December 2024. A total of 921 pregnancies were included, comprising 816 singleton pregnancies and 105 multiple pregnancies. Maternal and neonatal baseline characteristics were compared between ART-mediated and spontaneous conceptions within each gestational category. Outcomes assessed included postpartum hemorrhage (PPH), preterm birth (PTB), small for gestational age (SGA), neonatal intensive care unit (NICU) admission, 5-minute Apgar score < 7, and neonatal death. Multivariable logistic regression was performed to estimate adjusted odds ratios (aORs), controlling for relevant confounders. Results: Most maternal and neonatal outcomes did not significantly differ between ART-mediated and spontaneous conceptions in either singleton or multiple pregnancies. There were no statistically significant differences in the rates of PTB, SGA, NICU admission, low 5-minute Apgar score, and neonatal death between the groups. However, there was a significantly higher incidence of PPH in ART-conceived singleton pregnancies (25.7% vs. 9.4%), which remained significant in the multivariable analysis (aOR: 3.64, 95% confidence interval (CI): 2.21–5.98; p < 0.001). No significant difference in PPH incidence was observed in the multiple pregnancy cohort. Conclusions: Overall, most outcomes were comparable between ART-mediated and spontaneous conceptions. However, ART-conceived singleton pregnancies showed a significantly higher risk of PPH, even after adjusting for confounders. These findings underscore the need for heightened surveillance for PPH in ART-mediated singleton pregnancies, even in the absence of other risk factors.

Severe acute maternal morbidity in multiple pregnancies: a nationwide cohort study

To evaluate the differences in adrenal function between very low birth weight (VLBW) infants from singleton and multiple pregnancies. Forty infants of birth weights less than 1500 g underwent an ACTH test. Thirty infants born from singleton pregnancies (singleton group) and ten born from multiple pregnancies (multiple group) were enrolled. A baseline blood sample was drawn for cortisol measurement and thereafter serum cortisol was measured 1 and 2 h after an i.v. injection of ACTH. In multiple pregnancies, the median basal cortisol level of the infants was significantly lower than that in the singletons. The median cortisol level at 1 and 2 h after administration of ACTH was significantly lower in infants from multiple gestations than in singletons. Of infants from the multiple gestation group six, and of the singleton infants 12, had baseline cortisol levels lower than the reference values (P=0.48). One hour after ACTH stimulation all multiple and 53% of the singleton group infants showed a subnormal (<500 nmol/l, P=0.007) cortisol response. Two hours after ACTH, nine multiple group patients and 43% of the singletons had subnormal (<500 nmol/l, P=0.01) stimulated cortisol levels. We have concluded that VLBW infants from multiple gestations seem to be at an increased risk of insufficient postnatal adrenocortical function. In the future, specific attention should be paid to evaluate further newborn infants from multiple pregnancies with regard to a possible benefit of hydrocortisone substitution in stressful clinical situations.

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.

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.

Background/Objectives: Preterm birth remains a major cause of neonatal morbidity and mortality, particularly in multiple pregnancies and in cases of cervical shortening. While cervical cerclage is established in singleton pregnancies, its efficacy in multiple gestations remains uncertain. This study compares pregnancy and neonatal outcomes following second-trimester cerclage in singleton and multiple pregnancies with a short cervix. Methods: In this retrospective cohort study, 96 women underwent second-trimester cerclage at a tertiary perinatal center between 2020 and 2024. All had a cervical length ≤ 25 mm or prolapsed membranes without infection or premature rupture. Primary outcomes included term delivery rate, gestational age, mode of delivery, and neonatal outcomes; secondary outcomes comprised surgical complications and rehospitalization, defined as the need for renewed inpatient care due to threatened preterm labor or procedure-related complications. Results: In total, 79 singleton and 17 multiple pregnancies were analyzed. Term delivery occurred more often in singletons (54%) than multiples (18%, p = 0.006). Mean gestational age at birth was 258 ± 25 days in singletons versus 228 ± 28 days in multiples (p &lt; 0.001). Birth weight was significantly lower in multiples (1985 g vs. 2943 g; p &lt; 0.001), and neonatal infections were more frequent (53% vs. 26%; p = 0.008). Caesarean delivery was more common in multiples (82% vs. 33%; p &lt; 0.001). Apart from increased postoperative contractions in multiples (24% vs. 5%; p = 0.031), complication rates and rehospitalization (27% vs. 29%; p = 0.8) were similar. Conclusions: Second-trimester cerclage is less effective in preventing preterm birth in multiple pregnancies compared to singleton pregnancies; however, it appears to be associated with a stabilizing clinical course and may facilitate outpatient management in selected high-risk cases. These findings support individualized counseling and shared decision-making, particularly in multifetal gestations.

Proteolytic activity directed against insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is found in human pregnancy serum. We have investigated changes in this protease activity in pregnancies in which the fetus is small for gestational age and in multiple pregnancies. Maternal serum was obtained from 18 singleton pregnancies at 27 weeks gestational age (GA), and matched fetal serum was collected by cordocentesis. Fetuses were appropriate for GA (AGA; n = 6), small for gestational age (SGA) with evidence of uteroplacental insufficiency (UPI; starved SGA; n = 6), or SGA without UPI (nonstarved SGA; n = 6). In a second study, serum was obtained from women with singleton (n = 10), twin (n = 10), and higher multiple pregnancies (n = 10) at 9 weeks GA. All women with more than three fetuses underwent embryo reduction to 2 fetuses before 15 weeks gestation, when a second serum sample was obtained. Circulating IGF-I and IGF-II were measured by RIA, and IGFBP-3 was measured by both RIA and immunoradiometric assay. IGFBP-3 protease activity was assessed by Western ligand blotting after incubation with a normal nonpregnancy sera pool, immunoblotting, and specific protease assay. In the growth study, circulating maternal IGF-I and IGFBP-3 levels were not different in the three groups, but fetal IGF-I and IGFBP-3 levels were significantly lower in the UPI fetuses (IGF-I, 6.9 +/- 0.5 micrograms/L; IGFBP-3, 547 +/- 70 micrograms/L) than in either the nonstarved SGA fetuses (IGF-I, 27.8 +/- 6.3; IGFBP-3, 769 +/- 41 micrograms/L; P < 0.01) or the AGA fetuses (IGF-I, 39.4 +/- 3.4; IGFBP-3, 872 +/- 91 micrograms/L; P < 0.01). Maternal serum IGFBP-3 protease activity, measured by protease using [125I]IGFBP-3 as substrate, was increased in pregnancies complicated by UPI compared with GA-matched pregnancies in which the fetus was AGA or nonstarved SGA. No significant fetal serum protease activity was demonstrated. In the multiple pregnancies, IGFBP-3 rose significantly from 9-15 weeks GA in singleton (P = 0.005), twin (P = 0.004), and multiple (P = 0.007) pregnancies, and levels were higher in mothers of multiple pregnancies than in those of twin (P < 0.05) or singleton (P < 0.01) pregnancies at both 9 and 15 weeks GA. IGF-I levels were not different in the three groups and did not significantly increase between 9-15 weeks GA.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of the time interval from antenatal corticosteroid exposure to delivery on neonatal outcome of very low birth weight infants

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

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

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.

After completing this article, readers should be able to: 1. Describe the standard of care for prenatal corticosteroids for women in preterm labor prior to 34 weeks’ gestation. 2. Describe the effects of prenatal corticosteroids on the fetus. 3. List the preferred corticosteroid for prenatal treatments. 4. Explain the recommendation regarding not using repetitive courses of prenatal corticosteroids. Prenatal glucocorticoids are standard of care for women at high risk of preterm delivery prior to 34 weeks’ gestation because randomized, controlled trials and extensive meta-analyses demonstrate decreased death and improved outcomes, primarily related to less respiratory distress syndrome (RDS) and a decreased incidence of intraventricular hemorrhages (IVH) (Fig. 1). (1) However, it is worth remembering that the benefits of prenatal corticosteroids initially were demonstrated in 1972, and most of the trials were completed before 1985. Most infants in the trials were delivered after 28 weeks’ gestation and in the presurfactant era, when mortality rates for infants whose birthweights were less than 1 kg were high and when obstetric management differed from current practice. Maternal corticosteroid therapy is validated practice, but care strategies proven to be effective may lose effectiveness as other aspects of care change and the target population most likely to benefit changes. This review asks a series of questions to frame the overriding question of how antenatal corticosteroids should be used in 2006. Figure 1. Meta-analysis of randomized controlled trials of prenatal corticosteroids. Adapted from Crowley. (1) The current recommendations come from the 1994 National Institutes of Health (NIH) Consensus Conference and were reinforced by a second NIH Consensus Conference in 2000. (2) The key points from the guidelines are: 1. The benefits of prenatal corticosteroids outweigh any risks that have been identified. The benefits include decreased death and decreased incidence of RDS and IVH. 2. All fetuses at 24 to 34 weeks’ gestation are candidates …

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

Multiple pregnancies are an important topic of obstetrics as they are interesting and carry high risk. The increasing use of ultrasonography (USG) has made it possible to detect multiple pregnancies early. In the last 30 years, there has been a significant increase in the number of multiple pregnancies, especially in developed countries, with the increase in gestational age and the use of progressively developing assisted reproductive techniques (ART). Complications related to preterm birth and prematurity are observed with an increased frequency in these pregnancies. Therefore, multiple pregnancies constitute a process that should be monitored much more closely than singleton pregnancies due to many accompanying maternal and fetal complications. In this study, it was aimed to evaluate the maternal and fetal outcomes of multiple pregnancies with assisted reproductive techniques or spontaneous delivery in our clinic. Among all pregnant women who gave birth in our hospital between January 2018 and March 2022, 53 multiple pregnancies were included in the study. Maternal age, gestational week, delivery history, mode of delivery, birth weight and apgar scores (1st and 5th minutes) of the patients in the hospital database and file records were evaluated in terms of obstetric pathologies and perinatal outcomes. Level 1 and level 2 ultrasonography measurements and Doppler ultrasonography measurements of all patients were made by our radiology doctor in our hospital. Patient follow-ups were managed by the same gynecologist and obstetrician. There was no significant difference in the mean age of the participants according to birth weight, week of birth and mode of delivery (p&gt;0.05). There was a significant difference in the mean age of the participants according to the presence of maternal hypertension (p&lt;0.05). There was a statistically significant relationship between birth weight and multiple pregnancy status (p&lt;0.05). The rate of birth weight of &lt;1000 g and 1000-1500 g was higher in triplet pregnancies, and birth weight was found to be significantly lower than in twin pregnancies and this finding is consistent with the literature. There was a statistically significant relationship between the week of birth and multiple pregnancy status (p&lt;0.05). The frequency of delivery between 24-28 and 28-32 weeks in triplet pregnancies was found to be significantly higher than in twin pregnancies and this finding is consistent with the literature. There was no statistically significant relationship between the presence of maternal Diabetes Mellitus (DM) and Hypertension (HT) and twin and triplet pregnancies (p&gt;0.05). A statistically significant difference was found between twin pregnancy and triplet pregnancy in terms of both Apgar 1st Minute and Apgar 5th Minute scores (p&lt;0.05). Both Apgar scores were higher in twin pregnancies. In a similar study, a high correlation and a statistically significant relationship was found between the 1st and 5th minute Apgar scores and the week of birth. One of the most determining factors on perinatal morbidity in multiple pregnancies is chorionicity. Perinatal outcomes are particularly related to week of birth and chorionicity. The biggest limitation of our study is the lack of sonographic evaluation of chorionicity in our file record information. Therefore, the relationship between neonatal outcomes and chorionicity could not be evaluated in this study and this is considered a limitation of the study.

Time interval from late preterm antenatal corticosteroid administration to delivery and the impact on neonatal outcomes