Comparative analysis of risk factors for retinopathy of prematurity in single and multiple birth neonates.

AIM: To conduct a comparative analysis of risk factors for retinopathy of prematurity (ROP) in single- and multiple-born neonates. METHODS: In a retrospective evaluation of 521 premature neonates, encompassing singletons, twins, and triplets born at or before 34 weeks of gestational age with a birthweight of less than 2000 g and who completed the ROP screening program, between 2020 and 2023, in outpatient referral ROP screening clinic affiliated by Shiraz University of Medical Sciences, were included. Neonates with the eligibility criteria were enrolled in the screening program from 28 days old age and followed up to discharge or treatment based on national ROP screening guideline. Data on ROP severity, outcome, treatment modality, and risk factors, including gestational age (GA), birth weight (BW), sex, duration of neonatal intensive care unit (NICU) admission, oxygen supplementation, mechanical ventilation, blood transfusion, method of delivery, and maternal and neonatal comorbidities, were extracted and compared between premature neonates from singleton and multiple births. RESULTS: The analysis of the ROP severity distribution revealed 238 neonates (45.7%) with low-risk (type 2 prethreshold ROP or less severe) ROP and 16 (3.1%) with high-risk (type I prethreshold ROP or more severe) ROP who underwent treatment. According to the comparative analysis of risk factors in neonates with ROP requiring treatment, multiple birth neonates exhibited significantly greater GA (27.50 ± 3.27 vs. 30.00 ± 2.00 vs. 31.14 ± 0.38 weeks, p = 0.032 for singletons, twins and triplets, respectively); greater BW (861.67 ± 274.62 vs. 1233.33 ± 347.75 vs. 1537.14 ± 208.86 g, p = 0.002); and shorter duration of NICU admission (60.17 ± 21.36 vs. 34.00 ± 12.17 vs. 12.00 ± 6.32 days, p = 0.001) and oxygen supplementation (47.33 ± 16.57 vs. 36.00 ± 8.49 vs. 4.60 ± 2.41 days, p = 0.001). There was no significant difference between single-born neonates and multiple-born neonates regarding the prevalence of other risk factors. Multiple-born neonates with no ROP and low risk ROP showed significantly lower GA and BW compared to singletons (p < 0.001). CONCLUSION: Multiple gestation neonates may develop high-risk ROP requiring treatment at a greater gestational age and birth weight and at a lower duration of oxygen supplementation and NICU admission compared to the single birth neonates. This pattern prompts a reevaluation of screening criteria, suggesting a potential need to consider multiple birth neonates with lower traditional risk factors in screening programs. This pattern should be further evaluated in larger populations of multiple born premature neonates.

Maternal diabetes following gestational diabetes: Does multiple gestation multiply the risk?

OBJECTIVE: To assess whether the risk for future diabetes is higher among women diagnosed with gestational diabetes (GD) during twin versus singleton gestations. METHOD: A retrospective cohort study was performed including all women who delivered at a tertiary medical center between the years 1991 and 2021 and had at least one GD diagnosis. The first GD diagnosis per women was defined as the index pregnancy. Women diagnosed with GD during multiple gestations were compared with women diagnosed with GD during singleton gestations. The outcomes included first hemoglobin A1C (Hba1C) level > 6.4 mg/dL post partum, and the highest level measured during the follow-up period of up to 30 years. Multivariable logistic and Cox proportional analysis were used to compare the risk between the two groups while adjusting for confounding variables. RESULTS: The current study included 13 770 mothers, with 458 patients (3.3%) diagnosed with GD during twin gestations and 13 312 (96.7%) during singleton gestations. The mean follow-up was 12.25 ± 9.3 years. Mothers of both groups did not differ in age at index pregnancy; however, mothers of twins were more likely to conceive following fertility treatments. Incidence of diabetes and prediabetes (defined as Hba1C > 6.4 and >5.7, respectively) were lower among the twin-gestation group, both during the 6-month postpartum period (for diabetes: 15.5% vs 22.1%; odds ratio [OR], 0.65 [95% confidence interval (CI), 0.46-0.91]) and during the long-term follow-up (for diabetes: 31.8% vs 40.7%; OR, 0.68 [95% CI, 0.52-0.88]). These results remained significant in the multivariable analysis, while accounting for age, ethnicity, and fertility treatments. CONCLUSION: GD diagnosis during multiple versus singleton gestations is associated with a lower risk for future diabetes.

Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Recurrent preterm delivery following twin versus singleton preterm delivery: A retrospective cohort.

OBJECTIVE: The main risk factor for preterm delivery (PTD; <37 gestational weeks) is having a history of PTD. The aim of this research was to compare the risk for recurrent PTD following twin versus singleton gestation PTD. METHODS: A retrospective population-based cohort study was performed, including all women who had two consecutive pregnancies, the first of which ended with PTD. The incidence of PTD recurrence was compared between women with PTD in twin versus singleton gestation. Multivariable logistic models were used to study the association between twinning status and PTD recurrence, and specifically by gestational age of the first PTD, inter-pregnancy interval (IPI), and mode of conception. RESULTS: The study population included 15 590 women, of whom 1680 (10.8%) had twins in their index pregnancy and 13 910 (89.2%) had singletons. The incidence of recurrent PTD was 10.5% (n = 177) following twin PTD versus 21.9% (n = 3044) following singleton PTD (adjusted odds ratio = 0.50, 95% confidence interval 0.32-0.76, while controlling for confounding variables). The results were consistent while stratifying by IPI, gestational age of the first PTD, or mode of conception. CONCLUSIONS: Women with PTD in twin gestations are at lower risk for recurrent PTD compared with women with singleton PTD.

Fetal sexual dimorphism and preeclampsia among twin pregnancies.

Background: In singleton pregnancies, fetal sexual dimorphism has been observed in hypertensive disorders of pregnancy (HDP), particularly preeclampsia, a morbid syndrome that increases risk of adult onset cardiovascular disease for mothers and their offspring. However, few studies have explored the effect of fetal sex on HDP among twin pregnancies. Methods: We conducted a retrospective cohort study of 1,032 twin pregnancies between 2011 - 2022 using data from a perinatal database that recruits participants from three hospitals in Houston, TX. We categorized pregnancies based on fetal sex pairings into female/female, male/male, and female/male. Pregnancies with a female/female fetal sex were used as our reference group. Our primary outcomes included gestational hypertension, preeclampsia, superimposed preeclampsia, and preeclampsia subtyped by gestational age of delivery. A modified Poisson regression model with robust error variance was used to calculate the relative risk (RR) and 95% confidence interval (CI) for the association between fetal sex pairs and HDP. Results: Adjusted models of female/male fetal sex pairs were associated with preterm preeclampsia (RR 2.01, 95% CI 1.15-3.53) relative to those with female/female fetuses. No associations with other HDP were observed among pregnancies with male/male fetal sex compared to those with female/female fetal sex pairs. Conclusions: We found some evidence of sexual dimorphism for preterm preeclampsia among female/male twin pairs. Additional research is needed to understand what biological mechanisms could explain these findings.

Post Antenatal Late Preterm Steroids trial: interrupted time series analysis of respiratory outcomes in twin and pregestational diabetes.

BACKGROUND: The Antenatal Late Preterm Steroids trial found that corticosteroid administration decreased respiratory complications by 20% among late preterm singleton deliveries. After the Antenatal Late Preterm Steroids trial, corticosteroid administration increased by 76% among twin pregnancies and 113% among singleton pregnancies complicated by pregestational diabetes mellitus compared with expected rates based on the pre-Antenatal Late Preterm Steroids trial trend. However, the effect of corticosteroids on twin pregnancies and pregnancies complicated by pregestational diabetes mellitus is not well studied, as the Antenatal Late Preterm Steroids trial excluded twin pregnancies and pregnancies complicated by pregestational diabetes mellitus. OBJECTIVE: This study aimed to examine the change in the incidence rate of immediate assisted ventilation use and ventilation use for more than 6 hours among 2 populations after the dissemination of the Antenatal Late Preterm Steroids trial at the population level. STUDY DESIGN: This study was a retrospective analysis of publicly available US birth certificate data. The study period was from August 1, 2014, to April 30, 2018. The dissemination period of the Antenatal Late Preterm Steroids trial was from February 2016 to October 2016. Population-based interrupted time series analyses were performed for 2 target populations: (1) twin pregnancies not complicated by pregestational diabetes mellitus and (2) singleton pregnancies complicated by pregestational diabetes mellitus. For both target populations, analyses were limited to individuals who delivered nonanomalous live neonates between 34 0/7 and 36 6/7 weeks of gestation (vaginal or cesarean delivery). As a sensitivity analysis, a total of 23 placebo tests were conducted before (5 tests) and after (18 tests) the dissemination period. RESULTS: For the analysis of late preterm twin deliveries, 191,374 individuals without pregestational diabetes mellitus were identified. For the analysis of late preterm singleton pregnancy with pregestational diabetes mellitus, 21,395 individuals were identified. After the dissemination period, the incidence rate of immediate assisted ventilation use for late preterm twin deliveries was significantly lower than the expected value based on the pre-Antenatal Late Preterm Steroids trial trend (11.6% observed vs 13.0% expected; adjusted incidence rate ratio, 0.87; 95% confidence interval, 0.78-0.97). The incidence rate of ventilation use for more than 6 hours among late preterm twin deliveries did not change significantly after the dissemination of the Antenatal Late Preterm Steroids trial. A significant increase in the incidence rate of immediate assisted ventilation use and ventilation use for more than 6 hours was found among singleton pregnancies with pregestational diabetes mellitus. However, the results of placebo tests suggested that the increase in incidence was not necessarily due to the dissemination period of the Antenatal Late Preterm Steroids trial. CONCLUSION: The dissemination of the Antenatal Late Preterm Steroids trial was associated with decreased incidence of immediate assisted ventilation use, but no change in ventilation use for more than 6 hours, among late preterm twin deliveries in the United States. In contrast, the incidence of neonatal respiratory outcomes among singleton deliveries with pregestational diabetes mellitus did not decrease after the dissemination of the Antenatal Late Preterm Steroids trial.

Twins vs singletons-Long-term health outcomes.

INTRODUCTION: Multiple gestations are a risk factor for most pregnancy complications. The current study aimed to study whether offspring born after twin pregnancies are at increased risk for long-term health complications. MATERIAL AND METHODS: A retrospective cohort study was conducted in a large medical center, including all offspring born between the years 1991-2021, which were followed-up until 18 years of age. Hospital-based diagnoses of the offspring were categorized into main groups of morbidities: cardiac, respiratory, infectious, neurological, malignancy, and metabolic. Incidence of hospitalization with diagnoses from each main group was compared between twins and singletons, as well as time to first hospitalization. Cox proportional hazard models were used to study the association between twins vs singletons and hospitalizations by grouped morbidities, while adjusting for maternal age, ethnicity and gender, besides maternal recurrence in the cohort. RESULTS: A total of 369 478 offspring were included in the analysis; of these 11 986 (3.2%) were twins and 357 492 (96.8%) were singletons. Twins were more likely to be delivered preterm (odds ratio = 17.65, 95% CI: 16.74-18.60), by cesarean delivery and following infertility treatments. Incidence of hospitalizations with all morbidity groups was slightly, some significantly, higher among twins, including cardiac: 1.9% vs 1.5%, respiratory; 8.4% vs 7.1%, neurological: 7.7% vs 7.4%, infectious: 26.0% vs 24.1%, and malignancies: 0.7% vs 0.4%. The risk remained higher in the multivariable analyses (adjusted hazard ratios ranging between 1.09-1.75). When stratifying by gestational age at delivery, the risk for most morbidities was lower among twins vs singletons born in similar gestational ages. CONCLUSIONS: Twins as compared to singletons are at increased risk for most morbidities due to their risk of being born earlier.

Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations. DATA SOURCES: MEDLINE, Embase, LILACS, and CINAHL (from their inception to January 31, 2023), Cochrane databases, Google Scholar, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a twin gestation. METHODS: The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was preterm birth <34 weeks of gestation. Secondary outcomes included adverse perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in each included study, heterogeneity, publication bias, and quality of evidence, and performed subgroup and sensitivity analyses. RESULTS: Eleven studies (3401 women and 6802 fetuses/infants) fulfilled the inclusion criteria. Among all twin gestations, there were no significant differences between the vaginal progesterone and placebo or no treatment groups in the risk of preterm birth <34 weeks (relative risk, 0.99; 95% confidence interval, 0.84-1.17; high-quality evidence), <37 weeks (relative risk, 0.99; 95% confidence interval, 0.92-1.06; high-quality evidence), and <28 weeks (relative risk, 1.00; 95% confidence interval, 0.64-1.55; moderate-quality evidence), and spontaneous preterm birth <34 weeks of gestation (relative risk, 0.97; 95% confidence interval, 0.80-1.18; high-quality evidence). Vaginal progesterone had no significant effect on any of the perinatal outcomes evaluated. Subgroup analyses showed that there was no evidence of a different effect of vaginal progesterone on preterm birth <34 weeks of gestation related to chorionicity, type of conception, history of spontaneous preterm birth, daily dose of vaginal progesterone, and gestational age at initiation of treatment. The frequencies of preterm birth <37, <34, <32, <30, and <28 weeks of gestation and adverse perinatal outcomes did not significantly differ between the vaginal progesterone and placebo or no treatment groups in unselected twin gestations (8 studies; 3274 women and 6548 fetuses/infants). Among twin gestations with a transvaginal sonographic cervical length <30 mm (6 studies; 306 women and 612 fetuses/infants), vaginal progesterone was associated with a significant decrease in the risk of preterm birth occurring at <28 to <32 gestational weeks (relative risks, 0.48-0.65; moderate- to high-quality evidence), neonatal death (relative risk, 0.32; 95% confidence interval, 0.11-0.92; moderate-quality evidence), and birthweight <1500 g (relative risk, 0.60; 95% confidence interval, 0.39-0.88; high-quality evidence). Vaginal progesterone significantly reduced the risk of preterm birth occurring at <28 to <34 gestational weeks (relative risks, 0.41-0.68), composite neonatal morbidity and mortality (relative risk, 0.59; 95% confidence interval, 0.33-0.98), and birthweight <1500 g (relative risk, 0.55; 95% confidence interval, 0.33-0.94) in twin gestations with a transvaginal sonographic cervical length ≤25 mm (6 studies; 95 women and 190 fetuses/infants). The quality of evidence was moderate for all these outcomes. CONCLUSION: Vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients.

Perioperative Maternal-Fetal Outcomes in the Setting of Minimally Invasive Fetal Therapy for Complex Monochorionic Pregnancies with Monitored Anesthesia Care.

INTRODUCTION: Fetoscopic selective laser photocoagulation (FSLPC) and selective cord occlusion with radiofrequency ablation (RFA) can improve fetal outcomes when vascular anastomoses between fetuses cause twin-to-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) in multiple gestation pregnancies with monochorionic placentation. This study analyzed perioperative maternal-fetal complications and anesthetic management in a high-volume fetal therapy center over a 4-year period. METHODS: Included patients received MAC for minimally invasive fetal procedures for complex multiple gestation pregnancies between January 1, 2015, and September 20, 2019. Maternal and fetal complications, intraoperative maternal hemodynamics, medication usage, and reasons for conversion to general anesthesia, if applicable, were analyzed. RESULTS: A total of 203 (59%) patients underwent FSLPC and 141 (41%) had RFA. Four patients (2%; rate 95% CI: 0.00039, 0.03901) undergoing FSLPC had conversion to general anesthesia. No conversions to general anesthesia occurred in the RFA group. The incidence of maternal complications was higher in those who underwent FSLPC. No aspiration or postoperative pneumonia events were observed. Medication usage was similar in FSLPC and RFA groups. CONCLUSION: A low rate of conversion to general anesthesia and no serious adverse maternal events were observed in patients receiving MAC.

Is bigger better? A comparison of growth restriction rates using the crown-rump length derived due date from the smaller versus larger twin.

BACKGROUND: Although the smaller twin's crown-rump length is most accurate in establishing the estimated due date in dichorionic gestations, societal guidelines favor the use of the larger twin measurements based on concern for missing a diagnosis of fetal growth restriction. OBJECTIVE: This study aimed to compare the accuracy of the diagnosis of early- and late-onset fetal growth restriction in dichorionic twin gestations conceived by assisted reproductive technology using the estimated due date as established by the crown-rump length of the smaller vs larger twin. STUDY DESIGN: This was a 10-year retrospective cohort study of nonanomalous, dichorionic gestations conceived with assisted reproductive technology at 2 institutions. The incidence of early-onset (<32 weeks of gestation) and late-onset (≥32 weeks of gestation) growth restriction derived from the Hadlock formula using the smaller and larger crown-rump length estimated due date was compared with the true estimated due date by assisted reproductive technology. Statistical significance was determined using the Fisher exact test. The incidence of missed fetal growth restriction cases, false-positive rate, and error were calculated along with the relative risk for a missed diagnosis using the smaller crown-rump length. RESULTS: A total of 176 subjects were screened: 81 had a fetal growth ultrasound at 24 to <32 weeks of gestation, and 58 had a fetal growth ultrasound at ≥32 weeks of gestation. There was a significant difference in the incidence of fetal growth restriction using the 3 dating strategies in both gestational age ranges (P<.001) with the smaller crown-rump length estimated due date more closely approximating the true rate. Before 32 weeks of gestation, the smaller crown-rump length estimated due date missed 2.5% of fetal growth restriction cases, whereas the larger crown-rump length estimated due date missed 0.6% of fetal growth restriction cases, with false-positive and error rates of 1.2% and 3.7% and 5.5% and 6.2%, respectively. After 32 weeks of gestation, the smaller crown-rump length estimated due date missed 1.8% of cases, whereas the larger crown-rump length estimated due date missed 0% of cases, with false-positive and error rates of 2.6% and 4.4% and 5.3% and 5.3%, respectively. The relative risk for a missed diagnosis of fetal growth restriction using the smaller crown-rump length estimated due date was 1.77 for early-onset growth restriction and 1.22 for late-onset growth restriction. CONCLUSION: Using the estimated due date derived from the smaller twin led to a more accurate detection of fetal growth restriction at a cost of a higher missed diagnosis rate.

The influence of maternal respiratory allergy on obstetrics and perinatal outcomes: A nested case-control study.

OBJECTIVE: To evaluate the influence of respiratory allergy on obstetrics and perinatal outcomes. METHODS: A nested case-control retrospective study on 41 035 pregnant women. Obstetrics and perinatal outcomes of women with or without respiratory allergy were compared. Rates of preterm delivery (<37 weeks of gestation), low birth weight (<2500 g), neonatal acidosis (pH < 7.20), low 5-min APGAR score (<7), cesarean section rate and indications, and perinatal morbidity and mortality were analyzed. Results are expressed as number and percentages. χ2 and Fisher exact tests were used for comparisons. Logistic regression was used. Statistical significance was set at 95% level (P < 0.05). RESULTS: A total of 724 (1.8%) patients had respiratory allergy, and their rates of preterm delivery and low birth weight were significantly higher than those of control women (both P < 0.001). Nevertheless, analyzing the causes, multiple gestation rate was significantly higher in this group, and adjusting by this, no statistical difference was found in any of the perinatal outcomes studied. In addition, in vitro fertilization and sterility were also significantly higher in the respiratory allergy group (both P < 0.001). CONCLUSION: Women with respiratory allergy are at higher risks of prematurity and low birth weight but these results are mediated by sterility, in vitro fertilization, and multiple gestation rate. Nonetheless, participation of inflammatory mechanisms should be further studied.

Association of adverse pregnancy outcomes and multiple gestation with natural menopause: A population-based cohort study.

OBJECTIVE: Adverse pregnancy outcomes (APOs) and early menopause are each associated with increased risk of cardiovascular disease (CVD); whether APOs are associated with age at menopause is unclear. We examined the association of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and multiple gestation with age at natural menopause. STUDY DESIGN: Observational, prospective study within the Nurses' Health Study II cohort (1989-2019). MAIN OUTCOMES MEASURES: Risk of early natural menopause, defined as occurring before the age of 45 years, and age at onset of natural menopause (hazard ratio (HR) >1 indicates younger age at menopause). RESULTS: The mean [SD] baseline age of 69,880 parous participants was 34.5 [4.7] years. Compared with participants who had a term singleton first birth, those with a term multiple-gestation first birth had higher risk of early menopause (HR: 1.65, 95% CI: 1.05, 2.60) and younger age at natural menopause (HR: 1.46, 95% CI: 1.31, 1.63). Estimates for preterm multiple gestation were of similar magnitude. Menopause occurred at a younger age for those with a preterm birth with spontaneous labor (HR: 1.08, 95% CI: 1.03, 1.14) compared to those with a term birth with spontaneous labor. Conversely, estimates for GDM (HR: 0.95, 95% CI: 0.89, 1.02) and HDP (preeclampsia, HR: 0.93, 95% CI: 0.89, 0.97) suggested an association with older age at menopause. CONCLUSIONS: In this large cohort study, several statistically significant associations between APOs and age at natural menopause were observed. A deeper understanding of the relationships among APOs, menopause, and CVD is needed to help identify people at higher risk for early menopause and later CVD.

Adverse obstetric outcomes in women with PCOS and multiple gestations.

RESEARCH QUESTION: Does multiple gestation alter the risks for adverse obstetric outcomes in women with polycystic ovary syndrome (PCOS)? DESIGN: Retrospective population-based cohort study using data from the HCUP-NIS from 2004 to 2014. A total of 14,882 women with PCOS, who delivered within that time period, were identified. The study group comprised women with PCOS who had had a multiple gestation (n = 880); the reference group was comprised of the remaining women with PCOS and singleton gestation (n = 14,002). RESULTS: In women with PCOS, multiple gestation increased the risks of pregnancy complications including pregnancy-induced hypertension (adjusted odds ratio [aOR] 2.030; 95% confidence interval [CI] 1.676-2.460), pre-eclampsia (aOR 2.879; 95% CI 2.277-3.639), pre-eclampsia and eclampsia superimposed on pre-existing hypertension (aOR 1.917; 95% CI 1.266-2.903) and gestational diabetes (aOR 1.358; 95% CI 1.114-1.656). Multiple gestation increases the risk of preterm premature rupture of membranes (aOR 5.807; 95% CI 4.153-8.119), preterm delivery (aOR 8.466; 95% CI 7.071-10.135), Caesarean section (aOR 5.146; 95% CI 4.184-6.329), post-partum haemorrhage (aOR 1.540; 95% CI 1.065-2.228) and the need for transfusion (aOR 3.268; 95% CI 2.010-5.314), as well as wound complications (aOR 3.089; 95% CI 1.647-5.794). Neonates born to mothers with PCOS and having multiple gestations are more likely to be small for gestational age when compared to singleton neonates born to mothers with PCOS (aOR 4.606; 95% CI 3.480-6.095). Among PCOS women with multiple gestations, obesity increased the risks of developing pregnancy-induced hypertension (P < 0.001), pre-eclampsia (P < 0.001) and wound complications (P = 0.045). CONCLUSION: These results highlight the importance of single embryo transfer and ovulation induction to develop a single follicle in women with PCOS. Obesity further increases obstetrical complications.

A Case of a Negative Urine Pregnancy Test in a Multiple Gestation Pregnancy.

Urine pregnancy tests (UPTs) are a highly reliable method of detecting pregnancy, with reported 100% sensitivity and 99.2% specificity. This test relies on the detection of ß-human chorionic gonadotropin (ß-hCG) molecules in the urine through a two-site sandwich immunoassay. Although a nearly perfect test, it is common knowledge that this test can be falsely negative if performed too early in the pregnancy when urinary ß-hCG concentrations fall below detectable levels. Less commonly known is that the test may provide a false-negative result when urinary ß-hCG concentrations are extremely elevated, such as gestational trophoblastic disease or multiple gestations. Here, we present a case of a patient with a prior positive urine pregnancy test who presents with symptoms consistent with early pregnancy. Repeat testing resulted in a negative urine pregnancy test. Additional workup revealed significantly elevated serum quantitative ß-hCG and bedside ultrasound revealed multiple gestation intrauterine pregnancy. The patient ultimately delivered triplets by repeated caesarean section. It is important for physicians to understand and recognize the limitations of the urine pregnancy test in order to best facilitate care for patients who may have a false-negative pregnancy test result, as there are significant risks of improper patient management with a multiple gestation pregnancy or gestational trophoblastic disease.

Prevalence of and Risk Factors for Iron Deficiency in Twin and Singleton Newborns.

Iron deficiency (ID) in utero and in infancy can cause irreversible neurocognitive damage. Iron status is not routinely tested at birth, so the burden of neonatal ID in the United States is unknown. Infants born from twin or higher-order pregnancies may be at elevated risk of inadequate nutrient endowment at birth. The present study sought to compare the burden of neonatal ID in cord blood serum samples from twin (n = 54) and singleton pregnancies (n = 24). Iron status (serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) biomarker concentrations were measured by immunoassay. The prevalence of ID (SF < 76 ng/mL) among twins was 21% (23/108) and among singletons 20% (5/24). Gestational age at birth, maternal race and infant sex predicted SF levels. Maternal anemia (hemoglobin < 11 g/dL) was observed in 40% of mothers but was not associated with neonatal iron biomarkers. More research is needed to identify risk factors and regulatory mechanisms for inadequate fetal iron accrual to identify higher risk pregnancies and neonates for screening and intervention.

Placenta Accreta Spectrum Among Multiple Gestation: A Retrospective Analysis Based on a Chinese Population.

Background: It remained controversial whether women with multiple gestation are at higher risk of placenta accreta spectrum (PAS) disorders and large-scale studies are needed. This study aimed to assess whether PAS incidence is higher among women with multiple gestation than among singleton, as well as to compare the characteristics and outcomes of PAS in multiple and singleton gestation. Methods: Women who underwent cesarean section with live births at Peking University First Hospital from January 2015 to December 2020 were included. Demographic and clinical information was collected through chart review. Logistic regression models were used to analyze the associations between multiple gestation and PAS. The clinical characteristics and perioperative outcomes of PAS in multiple and singleton gestation were further compared. Results: Among the 14583 women included, 2.4% (352/14583) were diagnosed with PAS. PAS was slightly more prevalent among multiple gestations than among singletons (2.5% vs 2.4%, P=0.857). After adjusting for known risk factors and pregnancy complications, multiple gestation was associated with a higher risk of PAS (aOR=1.63, 95% CI 1.01-2.62). Among PAS patients, women who had multiple births had a significantly lower rate of previous cesarean deliveries (27.6% vs. 56.3%, P=0.003), placenta previa (17.2% vs. 56.3%, P<0.001) and invasive PAS (24.1% vs. 53.9, P=0.002) than singletons. There were no significant differences in perioperative outcomes between these two groups. Conclusion: Multiple gestation could be independently associated with an elevated risk of PAS. The clinical characteristics of PAS in the multiple and singleton gestation groups differed significantly in cesarean delivery history and placenta previa. The results of this study may inform guidelines on the screening, early detection and timely intervention of PAS patients among women with multiple births.

Evaluation of the predictive role of anterior uterocervical angle in preterm labor in twin gestation through meta-analysis: anterior uterocervical angle and preterm labor in twin gestation.

Multiple gestations are high-risk pregnancies with increased obstetric and perinatal risks. Preterm labor occurs in about half of twin pregnancies. Thus, prediction of the time of delivery and prevention of premature birth are very important in multiple gestations. Anterior uterocervical angle is a successful tool that has been used in the prediction of preterm labor in recent years. However there is only limited data about this issue for twin pregnancies in the literature. Here, we aimed to demonstrate the relationship between uterocervical angle and preterm labor in twin pregnancies more clearly and reliably with this meta-analysis. In this context, "twin gestation, uterocervical angle, cervical angle, angle, cervix, cervical, preterm and preterm labor" keywords were used and PubMed, Medline, ClinicalKey, Scopus, Science Direct, Web of Science, and Google Scholar database were searched between 1 January 2010 and 27 December 2020. Finally, a total of three studies were included in the analysis. Here, we found that uterocervical angle was associated with a higher risk of preterm delivery in the overall effect.

Complete Molar Pregnancies with a Coexisting Fetus: Pregnancy Outcomes and Review of Literature.

Objective The objective of the study was to review the obstetric outcomes of complete hydatidiform molar pregnancies with a coexisting fetus (CHMCF), a rare clinical entity that is not well described. Materials and Methods We performed a retrospective case series with pathology-confirmed HMCF. The cases were collected via solicitation through a private maternal-fetal medicine physician group on social media. Each contributing institution from across the United States ( n = 9) obtained written informed consent from the patients directly, obtained institutional data transfer agreements as required, and transmitted the data using a Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliant modality. Data collected included maternal, fetal/genetic, placental, and delivery characteristics. For descriptive analysis, continuous variables were reported as median with standard deviation and range. Results Nine institutions contributed to the 14 cases collected. Nine (64%) cases of CHMCF were a product of assisted reproductive technology and one case was trizygotic. The median gestational age at diagnosis was 12 weeks and 2 days (9 weeks-19 weeks and 4 days), and over half were diagnosed in the first trimester. The median human chorionic gonadotropin (hCG) at diagnosis was 355,494 mIU/mL (49,770-700,486 mIU/mL). Placental mass size universally enlarged over the surveillance period. When invasive testing was performed, insufficient sample or no growth was noted in 40% of the sampled cases. Antenatal complications occurred in all delivered patients, with postpartum hemorrhage (71%) and hypertensive disorders of pregnancy (29%) being the most frequent outcomes. Delivery outcomes were variable. Four patients developed gestational trophoblastic neoplasia. Conclusion This series is the largest report of obstetric outcomes for CHMCF to date and highlights the need to counsel patients about the severe maternal and fetal complications in continuing pregnancies, including progression to gestational trophoblastic neoplastic disease. Key Points CHMCF is a rare obstetric complication and may be associated with the use of assisted reproductive technology.Universally, patients with CHMCF who elected to manage expectantly developed antenatal complications.The risk of developing gestational trophoblastic neoplasia after CHMCF is high, and termination of the pregnancy did not decrease this risk.

Impact of advanced maternal age on maternal and neonatal outcomes in preterm birth.

OBJECTIVES: The aim of this study was to investigate the influence of advanced maternal age on the maternal and neonatal outcomes of preterm pregnancies. MATERIAL AND METHODS: The characteristics of patients admitted to the Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University between January 2015 and March, 2019 were retrospectively reviewed. The maternal and neonatal outcomes were compared between advanced maternal age group (≥ 35 years) and younger age group (18-34 years). Statistical analysis was performed by applying the SPSS software. RESULTS: The study population consisted of 986 pregnancies with preterm delivery and 1094 liveborn preterm infants. Multivariate analyses demonstrated that mothers of advanced age were more likely to suffer iatrogenic preterm birth, placenta previa, preeclampsia, gestational diabetes mellitus and postpartum hemorrhage, but less likely to suffer multiple gestation. In terms of neonatal outcomes, advanced maternal age was associated with a decreased rate of low birthweight in an adjusted model without multiple gestation. However, with multiple gestation included in the adjusted model, advanced maternal age was only associated with an increased rate of hyperbilirubinemia. CONCLUSIONS: Advanced maternal age was a risk factor for adverse pregnancy outcomes including iatrogenic preterm birth, placenta previa, preeclampsia, gestational diabetes mellitus, postpartum hemorrhage, and a protective factor for multiple gestation. Regarding neonatal outcomes, advanced maternal age was related to a decreased rate of low birthweight or an increased rate of hyperbilirubinemia depending on the adjustment for multiple gestation.

Clinical outcomes in higher-order multiples reduced to dichorionic diamniotic (DCDA) twins compared with primary twins and singletons: A prospective observational study.

OBJECTIVE: To compare outcomes in higher-order multiple pregnancies reduced to dichorionic diamniotic (DCDA) twins with primary DCDA twins and singleton pregnancies. METHODS: This prospective observational study included all higher-order multiple pregnancies that underwent ultrasound-guided transabdominal fetal reduction at 11-13 weeks of gestation from January 2018 to June 2020. Outcomes were compared with 100 primary DCDA twins and 1078 singletons. RESULTS: Sixty-four higher-order multiples underwent reduction at mean gestational age of 11.46 weeks. Of the reduced pregnancies, 3.12% resulted in miscarriage before 24 weeks compared with 2% (2/100) of primary twins and 0.74% of singletons (P = 0.09). The mean gestational age at delivery was 33.48 weeks for reduced twins, 34.52 weeks for primary twins (P = 0.10) and 38.14 weeks for singletons (P < 0.001). Compared with primary twins, the adjusted odds of preterm delivery before 34 weeks and before 36 weeks for reduced twins were 0.56 (95% confidence interval [CI] 0.48-3.54, P = 0.62) and 0.84 (95% CI 0.78-8.85, P = 0.08), respectively. There was no significant difference in rates of pre-eclampsia, Cesarean delivery, birth weight below the 10th and 3rd centiles, and perinatal mortality among primary and reduced twins. All risks were significantly lower in singleton pregnancies. CONCLUSION: Reduced twins have similar obstetric and perinatal outcomes as primary twins, but adverse outcomes are significantly higher in both groups when compared with singleton pregnancies.