The association between neonatal birthweight discordance and preeclampsia in twin pregnancy.

PURPOSE: To investigate the association between neonatal birthweight (NBW) discordance and preeclampsia (PE) in twin pregnancy. METHODS: This was a single-center retrospective cohort study. Women with two live births in the First Affiliated Hospital of Sun Yat-sen University from January 2011 to June 2020 were eligible. They were classified into four groups based on the quartiles of NBW discordance in monochorionic (MC) and dichorionic (DC) twin pregnancy. The relationship between NBW discordance and the risk of PE was assessed by logistic regression, subgroup analyses was further analyzed. RESULTS: A total of 1566 women were eligible for the final analysis, there were 445 MC cases and 1121 DC cases. No matter in monochorionic or dichorionic pregnancy, higher NBW discordance quartiles were associated with increased risks of PE. Compared with women in the lowest NBW discordance quartile, women in the highest NBW discordance quartile had approximately 3.6 and 6.0 times risk of PE in monochorionic and dichorionic pregnancy respectively. The association between quartiles of NBW discordance and the risk of PE were higher in dichorionic pregnancy than in monochorionic pregnancy. No matter in MC or DC pregnancy, no significant interaction effects were identified for maternal age, pregnancy body mass index, mode of conception and whether complicated with gestational diabetes mellitus. CONCLUSIONS: The increased NBW discordance quartile was related to an increased risk of PE. Assessing estimated fetal weight discordance by using ultrasound in clinical practice to predict PE remained to be further researched.

Velamentous cord insertion in monochorionic twin pregnancies: a step forward in screening for twin to twin transfusion syndrome and birthweight discordance?

OBJECTIVES: Two major complications of monochorionic diamniotic (MCDA) twin pregnancies are twin to twin transfusion syndrome (TTTS) and birthweight discordance. The current screening ultrasound test for these pathologies combines the detection of nuchal translucency discrepancy and abnormal ductus venosus in at least one twin, in the first trimester. We aim to determine whether combining the presence of velamentous cord insertion in at least one twin increases screening efficiency. METHODS: This was a retrospective cohort with a sample of 136 MCDA twin pregnancies followed at Centro Hospitalar Universitário São João, during a 16-year period. RESULTS: The combination of abnormal ductus venosus in at least one twin and nuchal translucency discrepancy is associated with the development of TTTS with an OR of 10.455, but not with birthweight discordance. The combination of these first trimester markers with velamentous cord insertion is not associated with the development of either outcome. CONCLUSIONS: The presence of velamentous cord insertion in MCDA pregnancies is not associated to TTTS development. Therefore, the addition of this marker to the first trimester screening would not effectively predict the development of birthweight discordance or TTTS. However, a positive currently used screening test increases the risk of developing TTTS by about ten times.

Impact of placental sharing and large bidirectional anastomoses on birthweight discordance in monochorionic twins: a retrospective cohort study in 449 cases.

BACKGROUND: In monochorionic twin pregnancies, the fetuses share a single placenta. When this placenta is unequally shared, a discordant antenatal growth pattern ensues resulting in high rates of perinatal morbidity and mortality. Understanding placental pathophysiology is paramount in devising feasible antenatal management strategies. Unequal placental sharing is not the sole determinant of birthweight discordance as there is no one-to-one relationship with placental share discordance. Placental angioarchitecture, especially the presence of large bidirectional anastomoses, is thought to affect this relationship by allowing for a compensatory intertwin blood flow. OBJECTIVE: This study aimed to assess whether placental angioarchitecture can affect birthweight discordance in live-born monochorionic twins, the aim of our study was 2-fold: (1) to assess the relationship between birthweight discordance and placental share discordance and (2) to examine to what extent large bidirectional anastomoses can compensate for the effect of unequal placental sharing on birthweight discordance, with a subgroup analysis for umbilical artery Doppler flow patterns in cases with a birthweight discordance of ≥20%. STUDY DESIGN: This was a retrospective cohort study that included monochorionic twin pregnancies observed in our center between March 2002 and June 2021, in which twins with a birthweight discordance of ≥20% were classified according to umbilical artery Doppler flow patterns of the smaller twin. We excluded cases with twin-twin transfusion syndrome and twin anemia polycythemia sequence. Monochorionic placentas of live-born twins were injected with dye, and images were saved for computer measurements of placental sharing and the diameter of anastomoses. Univariate linear regressions of the relationship between placental share discordance and birthweight discordance (both calculated as larger weight or share-smaller weight or share/larger weight or share×100%) and the relationship between arterioarterial and venovenous diameters and birthweight ratio/placental territory ratio were performed. RESULTS: A total of 449 placentas were included in the analysis. Placental share discordance was positively correlated with birthweight discordance (ß coefficient, 0.325; 95% confidence interval, 0.254-0.397; P<.0001). The arterioarterial diameter was negatively correlated with birthweight ratio/placental territory ratio (ß coefficient, -0.041; 95% confidence interval, -0.059 to -0.023; P<.0001), meaning that an increase in arterioarterial diameter leads to less birthweight discordance than expected for the amount of placental share discordance. There was no relationship between venovenous diameter and birthweight ratio/placental territory ratio (ß coefficient, -0.007; 95% confidence interval, -0.027 to 0.012; P=.473). CONCLUSION: Birthweight discordance in monochorionic twins was strongly associated with placental share discordance. Large arterioarterial anastomoses can mitigate the effect of unequal placental sharing.

Assessment of different thresholds of birthweight discordance for early neonatal outcomes: retrospective analysis of 2348 twin pregnancies.

BACKGROUND: The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy. METHODS: This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy. RESULTS: Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526-0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR+) = 5.77]. CONCLUSION: Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations.

The association between maternal and foetal factors with birth weight discordance in twins from Yucatan, Mexico.

Birth weight discordance (BWD) is not an uncommon event in twin pregnancies and can be associated with maternal and newborn characteristics. We aimed to analyse the association between maternal sociodemographic and newborn characteristics with BWD in twin infants born in Yucatan, Mexico, during 2008-2017 (n = 2091 pairs). BWD was calculated as the percentage of birth weight of the heavier twin. We defined three categories of BWD: concordant twins: <15%, mild-discordant: 15-24%, and severe discordant: ≥25%. A multinomial logistic regression model was used to analyse the association between maternal sociodemographic and newborn characteristics with BWD. Seventy-four percent (n = 1547) of twin pairs were classified as concordant, 17% (n = 356) met the criteria for mild-discordance and 9% (n = 188) for severe discordance. The odds for mild-discordance were significantly lower for mothers with medium level of education and in the highest quartile of total twin birth weight (TBW). Opposite-sex twin pairs showed increased odds for mild-discordance compared with same-sex pairs. The odds for severe discordance increased as mothers were in older age groups and decreased as TBW increased. Our rates of BWD are similar to those reported in populations from wealthier countries and maternal age and education, infants' sex, and TBW are associated with BWD.

Birthweight discordance and neonatal morbidity in twin pregnancies: A systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review was to quantify the association between birthweight discordance and neonatal morbidity in twin pregnancies. MATERIAL AND METHODS: MEDLINE, Embase and Cinahl databases were searched. Studies reporting the occurrence of morbidity in twins affected compared with those not affected by birthweight discordance were included. The primary outcome was composite neonatal morbidity (including neurological, respiratory, infectious morbidities, abnormal acid-base status and necrotizing enterocolitis). The secondary outcomes were the individual morbidities. Sub-group analysis according to chorionicity, gestational age at birth and fetal weight (smaller vs larger twin) was also performed. Random-effect head-to-head meta-analyses were used to analyze the data. RESULTS: Twenty studies (10 851 twin pregnancies) were included. The risk of composite morbidity was significantly higher in the pregnancies with birthweight discordance ≥15% (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.0-1.9), ≥20% (OR 2.2, 95% CI 1.40-3.45), ≥25% (OR 2.5, 95% CI 1.8-3.6), and ≥30% (OR 3.4, 95% CI 2.2-3.2). In dichorionic twins, birthweight discordance ≥15% (OR 2.4, 95% CI 1.65-3.46), ≥20% (OR 2.2, 95% CI 1.3-3.8), ≥25% (OR 2.7, 95% CI 1.4-5.1) and ≥30% (OR 3.6, 95% CI 2.3-5.7) were all significantly associated with composite neonatal morbidity. Analysis of monochorionic twins was hampered by the very small number of included studies, which precluded adequate statistical power. Monochorionic twins with a birthweight discordance ≥20% were at significantly higher risk of composite neonatal morbidity (OR 2.2, 95% CI 1.1-4.9) compared with those presenting with lesser degree of discordance. When stratifying the analysis according to gestational age at birth and fetal size, twins with birthweight discordance ≥15%, 20%, 25% and 30% delivered at ≥34 weeks were at higher risk of neonatal morbidity compared with controls, but there was no difference in the risk of morbidity between the larger and the smaller twin in the discordant pair. CONCLUSIONS: Birthweight discordance is associated with neonatal morbidity in twin pregnancies. The strength of this association persists for dichorionic twins. It was not possible to extrapolate robust evidence on monochorionic twins due to the low power of the analysis due to the small number of included studies.

Roles of venovenous anastomosis and umbilical cord insertion abnormalities in birthweight discordance in monochorionic-diamniotic twin pregnancies without twin-twin transfusion syndrome.

AIM: We evaluated risk factors for birthweight discordance in monochorionic diamniotic (MCDA) twin pregnancies without twin-twin transfusion syndrome (TTTS). METHODS: We investigated all MCDA twin placentas injected with colored dye at our institution between 2007 and 2015. We excluded pairs of twins with TTTS, fetal demise, or severe fetal malformation. All pairs of twins were assigned to the discordant group (birthweight discordance ≥ 25%) or the concordant group (birthweight discordance < 25%). In each pair of twins, we described vascular anastomoses as either arterioarterial, venovenous (VV), or arterial-venous, and abnormal umbilical cord insertion as either marginal or velamentous. We also recorded placental sharing discordance. RESULTS: A total of 150 placentas were analyzed. The incidence of VV anastomosis in the discordant group (40%) was significantly higher than that in the concordant group (12%, P = 0.005). Unilateral abnormal umbilical cord insertion was significantly more common in the discordant group (85%) than in the concordant group (38%, P < 0.001). Placental sharing discordance was seen more frequently in the discordant group than in the concordant group. Multiple logistic analysis revealed that VV anastomosis (odds ratio: 4.7; 95% confidence interval: 1.2-18.6, P < 0.01) and unilateral abnormal umbilical cord insertion of the smaller twin (odds ratio: 5.7; 95% confidence interval: 1.4-22.9, P < 0.01) were independent risk factors for birthweight discordance. CONCLUSION: VV anastomoses and unilateral abnormal umbilical cord insertion of the smaller twin are independent risk factors for birthweight discordance in MCDA twin pregnancies without TTTS.

Short- and long-term perinatal outcome in twin pregnancies affected by weight discordance.

INTRODUCTION: The objective was to investigate the association between chorionicity-specific intertwin birthweight discordance and adverse outcomes including long-term follow up at 6, 18, and 48-60 months after term via Ages and Stages Questionnaire. MATERIAL AND METHODS: In this secondary analysis of a cohort study (Oldenburg et al., n = 1688) and a randomized controlled trial (PREDICT study, n = 1045) twin pairs were divided into three groups according to chorionicity-specific birthweight discordance: <75th percentile, 75th-90th percentile and >90th percentile. Information on infant mortality, admittance to neonatal intensive care units, and gestational age at delivery was available for all pairs. Detailed neonatal outcomes were available for 656 pairs from PREDICT, of which 567 pairs had at least one Ages and Stages Questionnair follow-up. Logistic regression models were used for dichotomous outcomes. Ages and Stages Questionnair scores were compared using the method of generalized estimating equation to account for the correlation within twins. RESULTS: The 75th and 90th percentiles for birthweight discordance were 14.8 and 21.4% for monochorionic and 16.0 and 23.8% for dichorionic twins. After adjustment for small for gestational age and gender, birthweight discordance >75th and >90th percentile was associated with induced delivery <34 weeks [odds ratio 1.71 (95% confidence interval 1.11-2.65) and odds ratio 2.83 (95% confidence interval 1.73-4.64), respectively]. Discordance >75th-percentile was associated with an increased risk of infant mortality after 28 days [odds ratio 4.69 (95% confidence interval 1.07-20.45)] but not with major neonatal complications or with low mean Ages and Stages Questionnair scores at 6, 18, and 48-60 months after term. CONCLUSION: Chorionicity-specific intertwin birthweight discordance is a risk factor for induced preterm delivery and infant mortality, but not for lower scores for neurophysiological development at 6, 18, and 48-60 months.

[Singleton and twin pregnancies of PKU patients - individual variability of phenylalanine tolerance: experience of a single treatment center (Preliminary report)].

Phenylketonuria (PKU) is the autosomal recessive deficiency of phenylalanine hydroxylase resulting in the accumulation of phenylalanine (Phe) in blood and in the brain. Phe restriction in a patient's diet is determined depending on the amount of Phe intake which allows for stable blood Phe levels within the therapeutic range of 120-360µmol/L. In clinical practice the empirical determination of Phe tolerance relies on frequent assessment of blood Phe concentrations in relation to Phe intake from food records. Untreated maternal PKU may lead to maternal PKU syndrome in offspring. The objective of the study was to compare Phe tolerance during the course of singleton and multiple pregnancies of PKU patients. Case subjects and methods: The cases reviewed included three sets of classical PKU-affected Polish women on a low-phenylalanine diet during the course of singleton and twin pregnancies and their PKU-unaffected newborns. All the patients were under regular supervision of a metabolic dietitian to stabilize blood Phe levels and determine Phe tolerance. Data on pregnancy weight gain, the gestational age when the diet initiated, the percent of Phe assessments < 120 µmol/L and > 360 µmol/L, as well as offspring birth measurements were analyzed. RESULTS: The total increase in Phe tolerance and its pattern during the course of singleton and twin pregnancies differed remarkably in each patient. Three PKU women (Q383X/R408W, EX3DEL/EX3DEL, R281L/R408W) increased their Phe tolerance in singleton and twin pregnancies by 579%/468%, 674%/261%, and 427%/236%, respectively. During the last 10 weeks of singleton and twin pregnancy Phe tolerance showed an increase by 62%/149%, 33%/64%, and 37%/40%, respectively. The analysis of predictors for Phe tolerance showed that an individual's weight gain and the fetal weight gain as estimated from liveborn birth-weight data had no predictive capacity. CONCLUSIONS: Individual Phe tolerance in singleton pregnancies of PKU patients does not predict tolerance in twin pregnancy. Further research on the growing population of multiple pregnancy PKU patients is necessary to provide evidence-based guidelines to optimize the treatment of PKU in females of childbearing age.

Artery-to-vein anastomoses in unequally divided placentas and their association with birthweight discordance.

INTRODUCTION: This study investigated the impact of the shared intertwin circulation in unequally divided monochorionic (MC) placentas on fetal growth. METHODS: This retrospective analysis included color-dyed, unequally shared placentas from two tertiary centers. Exclusions included twin-twin transfusion syndrome, twin anemia polycythemia sequence, and lethal anomalies. Measurement of the external diameters and areas of the artery-to-artery (AA), artery-to-vein (AV), and vein-to-vein (VV) anastomoses was performed. The ratio of the shared circulation (AV ratio) was determined by comparing the areas of the summed venous components of shared AV anastomoses to those in the individual AV anastomoses of the smaller placental part. The birth weight ratio/placental ratio (BWR/PR), total AV size areas and net AV transfusion were calculated. Univariable and multivariable linear regressions were performed to assess the relationship between BWR/PR, the AV ratio, the areas of the different anastomoses and cord insertion discordance. RESULTS: Among 352 placentas, 97 % (340) had intertwin AV anastomoses, and 50 % (176) were from pregnancies with selective growth restriction. The AV ratio, AA, VV, total AV areas, and cord insertion discordance negatively correlated with BWR/PR. Multivariable linear regression confirmed the independent negative association between BWR/PR and the AV ratio, suggesting that a larger shared circulation benefits the twin with the smaller placental part. Type III sFGR placentas exhibited the highest AV ratio, resulting in the lowest BWR/PR. DISCUSSION: A larger shared circulation mitigates the impact of an unequally divided placenta on fetal growth. This effect surpasses the influence of AA and VV diameters and is most prominent in Type III sFGR placentas.

Can maternal serum midkine level predict chorionicity in twin pregnancies?

Sometimes it can be difficult to chorionicity determination in twin pregnancies. This study aimed to compare maternal serum midkine levels between twin and singleton pregnancies. We also evaluated the relationship between chorionicity and maternal serum midkine level in twin pregnancies. The present prospective cohort study included 16 patients with monochorionic diamniotic twin pregnancies, 38 with dichorionic diamniotic twin pregnancies, and 66 healthy singleton pregnancies admitted to Ankara City Hospital Perinatology Clinic between June 2021 and June 2022. Demographic features, clinical characteristics, and serum midkine levels were compared between the groups. Additionally, a receiver operator characteristics (ROC) analysis was performed to assess the performance of midkine for detecting chorionicity. The median maternal serum midkine level was found to be 0.64 ng/ml in twin pregnancies and 0.26 ng/ml in singleton pregnancies (p < 0.001). When twin pregnancies were compared in terms of chorionicity, serum midkine level was determined as 1.20 ng/ml in the monochorionic diamniotic group and 0.50 ng/ml in the dichorionic diamniotic group (p = 0.034). An optimal cut-off value of 1.03 ng/ml was found for the determination of chorionicity (AUC: 0.68, p = 0.03, 95% CI: 0.53-0.83, %56.3 sensitivity, 76.3% specificity). In advanced weeks of pregnancy, biomarkers can be used as helpful parameters for ultrasonography in the diagnosis of twin pregnancies. Maternal serum midkine levels might be used to determine chorionicity in equivocal cases.

Role of birthweight discordance in preterm twins' outcomes in the Korean neonatal network.

BACKGROUND: Twin pregnancies can be complicated by birthweight (BW) discordance. We analyzed the impact of BW discordance on clinical outcomes of very-low-birthweight (VLBW) twins. METHODS: The study population was preterm infants in the Korean Neonatal Network registry. Multivariate logistic regression analyses were used to determine the contribution of BW discordance on respiratory morbidities and mortality of VLBW infants. Also, we assessed the effect of small for gestational age (SGA) on morbidity and mortality in discordant twins (DTs) and compared separately the clinical outcomes of smaller and larger DTs with different singletons matched for perinatal factors including BW percentile. RESULTS: A total of 935 twin pairs [1548 concordant twins (CTs) and 322 DTs] were included. BW discordance was associated with increased odds of moderate bronchopulmonary dysplasia, mortality, and composite outcomes. Compared with the CTs, the smaller, but not larger, DTs had greater odds of morbidities and mortality. DTs had higher odds of adverse neonatal outcome when combined with SGA. Meanwhile, DTs had morbidities and mortality similar to singletons matched for BW percentile. CONCLUSION: BW discordance in VLBW twins adversely affects neonatal mortality or respiratory morbidity which is predominant in smaller DTs. The impact of BW discordance could be increased through SGA.

Impact of Gestational Diabetes and Hypertension Disorders of Pregnancy on Neonatal Outcomes in Twin Pregnancies Based on Chorionicity.

OBJECTIVES: The objective of this study was to investigate the impact of the co-existence of gestational diabetes (GDM) and hypertension disorders of pregnancy (HDP) on neonatal outcomes in twin pregnancies based on chorionicity. METHODS: A retrospective study of 1398 women with twin pregnancies was performed between January 2016 and December 2021. The effects of GDM and HDP on neonatal outcomes were assessed by logistic regression models. An additional stratified analysis was conducted to estimate the effects based on chorionicity (monochorionic (MC) and dichorionic (DC)). RESULTS: The incidence of the co-existence of GDM and HDP was 3.8%. The presence of GDM increased the likelihood of HDP only in women with MC twin pregnancies (OR, 2.13; 95% CI 1.08-4.19). After adjustments, co-existence of GDM and HDP was positively associated with gestational age (ß, 1.06; 95% CI 0.43-1.69) and birthweight (ß, 174.90; 95% CI 8.91-340.89) in MC twin pregnancies, while no associations were found between co-existence of GDM and HDP and neonatal outcomes in DC twin pregnancies. However, HDP was negatively associated with birthweight (ß, -156.97; 95% CI (-257.92, -56.02)) and positively associated with small-for-gestational-age (SGA) (OR, 2.03; 95% CI 1.02-4.03) and discordant twins (OR, 2.83; 95% CI 1.78-4.48) in DC twin pregnant women without GDM. CONCLUSIONS: Our results suggested that GDM leads to an increased risk of HDP only in MC twin pregnancies, but GDM seemed to attenuate the adverse effects of HDP on perinatal outcomes in both MC and DC twin pregnancies. Further investigation is needed to explain these intriguing findings.

Gestational hypertensive disease and birthweight discordance in twin pregnancies: a systematic review and meta-analysis.

INTRODUCTION: The objective of this systematic review was to explore the association between gestational hypertensive disease (GHD) and birthweight discordance in twin pregnancies. METHODS: PubMed, Embase, Web of Science and Cochrane Library were systematically searched for studies reporting the risk of birthweight discordance in twin pregnancies complicated compared with those not complicated by GHD from establishment until July 2021. Risk of bias was assessed with the Newcastle-Ottawa Scale. According to the classification of GHD, sub-group analyses reporting cases with gestational hypertension (GH), chronic hypertension (CH) and preeclampsia (PE) were performed separately. Stratification by twin chorionicity (dichorionic (DC) and monochorionic (MC)) was also conducted. When there was substantial heterogeneity (I2 ≥ 50%), the random effect mode was used to estimate the pooled risk ratio, otherwise the fixed effect model was used. RESULTS: Nine studies (303,204 twin pregnancies) were included. GHD (OR 1.45, 95% CI 1.41-1.49) was a risk factor for intertwin birthweight discordance [PE (OR 1.69, 95% CI 1.33-2.16); CH (OR 1.59, 95% CI 1.46-1.73); GH (OR1.45, 95%Cl 1.10-1.92]. After stratification, birthweight discordance was related to GHD (OR 2.51, 95% CI 2.01-3.14), GH (OR 2.08, 95% CI 1.33-3.25) and PE (OR 2.74, 95% CI 2.09-3.61) in DC pregnancies, but no longer associated with GHD and PE in MC group. CONCLUSIONS: Twin gestations complicated with GHD, especially in DC pregnancies, were at significantly higher risk of birthweight discordance.

The association of hypertensive disorders of pregnancy with small for gestational age and intertwin birthweight discordance.

Available evidence shows conflicting results regarding the association between hypertensive disorders of pregnancy (HDPs)/preeclampsia (PE) and small for gestational age (SGA) and birthweight discordance (BWD). This retrospective study of 2131 twin pregnancies aimed to evaluate the association of HDPs/PE with the presence of SGA and BWD. The eligible pregnancies were categorized into four study groups: concordant pairs without SGA fetuses, discordant pairs without SGA fetuses, concordant pairs with SGA fetuses, and discordant pairs with SGA fetuses. We applied binary logistic regression models to compare the incidence of HDPs/PE and multinomial logit regression models to evaluate the severity of PE between the study groups. The models were adjusted for potential confounders. Increases in HDPs were observed in concordant (aOR, 2.33; 95% CI: 1.46-3.73) and discordant (aOR, 3.50; 95% CI: 2.26-5.43) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.42; 95% CI: 0.81-2.49); increases in PE were also found in concordant (aOR, 1.87; 95% CI: 1.08-3.23) and discordant (aOR, 3.75; 95% CI: 2.36-5.96) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.34; 95% CI: 0.71-2.52). Discordant pregnancies with SGA fetuses were associated with severe PE (aRRR, 3.48; 95% CI: 1.79-6.77), whereas concordant pregnancies with SGA fetuses were associated with only mild PE (aRRR, 2.54; 95% CI: 1.33-4.88). Our results suggest that SGA is associated with the development of HDP/PE, while discordant growth is associated with the severity of PE. These associations need to be further investigated using estimated fetal weight (EFW).

Growth patterns and associated risk factors of congenital malformations in twins.

BACKGROUND: The rate of twinning continues to increase due to the combined effect of a rise in parental age and increased use of assisted reproductive technology. The risk of congenital anomalies in twins is higher than in singletons, but it is less well reported in relation to growth patterns. We focused to the auxological outcome of twin pregnancies when one or both of twins are affected by one or more malformations. METHODS: We conducted a retrospective observational study reviewing the clinical charts of twins admitted in the period between January 2003 and December 2018 at the University Hospital of Palermo. The associations between malformations and anthropometric variables at birth were analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins. RESULTS: We studied data of 488 neonates (52% females) from 244 pregnancies. The rate of major congenital anomalies was 11%, affecting significantly the smaller twin (p = .00018; Odds ratio 3.21; 95% CI 1.65 6.59). Malformation class distribution was as following: genitourinary (24%), gastrointestinal (20%), cardiovascular (18.5%), musculoskeletal (11%), central nervous system (9%), syndromic (9%), ocular (5.5%) and diaphragmatic hernia (2%). The most predictive value, the Birthweight (BW) difference mean ratio in malformed versus not malformed neonates (- 0.31 vs 0.02; p = .0016) was distributed equally lower than zero in all malformed twins, except for those with congenital heart defects (p = .0000083). Microcephaly (head circumference < 2 standard deviation, SD) was present in 3% of symmetrically smaller twin, and severe microcephaly (< 3 SD) was present in 0.6%. We found that an intertwin BW discordance of 18% or greater identified 50% of neonates with microcephaly, but only 11% of malformed twins. CONCLUSIONS: In case of one twin with a BW < 10th centile, a concomitant intertwin BW discordance ≥18% could reveal an increased risk for microcephaly but not for malformation. Lower values of BW, Ponderal index, Body mass index but above all negative value of BW difference mean ratio are associated with malformations in twin pairs.

Role of velamentous cord insertion in monochorionic twin pregnancies: a PRISMA-compliant systematic review and meta-analysis of observational studies.

Background: Velamentous cord insertion (VCI) has been proposed to be associated with some specific complications among monochorionic (MC) twin pregnancies. This meta-analysis and systematic review aims to determine the role of VCI in MC twin pregnancies.Methods: The PubMed, Embase and Web of Science databases and reference lists were searched for relevant studies. Outcomes of interest included twin-to-twin transfusion syndrome (TTTS), birthweight discordance (BWD) and selective intrauterine growth restriction (sIUGR). The methodological quality of the included studies was assessed by using the Newcastle-Ottawa Scale. The pooled results were calculated by means of a random or fixed effect model to obtain odds ratio with 95% confidential interval (CI). Subgroup analyses were utilized to detect the sources of heterogeneity.Results: Twenty studies were eligible for inclusion. The pooled result suggested a significant association between VCI and TTTS (OR, 1.542; 95% CI, 1.116-2.129) with a moderate level of heterogeneity (Q test: p = .024; I2 = 50.2%). Subgroup analysis reported single-center study, methodological quality and exclusion of laser-coagulated TTTS as the sources of heterogeneity. Another analysis revealed an increased risk of BWD among twin pregnancies with VCI (OR, 2.945; 95% CI, 2.176-3.984) with a low heterogeneity (Q test: p = .347; I2 = 10.5%). None of study level characteristics was found to be an influencing factor. Three studies reporting on sIUGR suggested a significant association between VCI and sIUGR.Conclusions: The meta-analysis and systematic review suggests an association between VCI and BWD and sIUGR. However, the association between VCI and TTTS may be overestimated and high-quality studies with a representative sample are needed in further research.

Are Twin Pregnancies Complicated by Weight Discordance or Fetal Growth Restriction at Higher Risk of Preeclampsia?

Studies have reported controversial findings on the association between fetal growth restriction (FGR) or intertwin weight discordance and the risk of hypertensive disorders of pregnancy (HDP) in twin pregnancies. The aim of this study was to investigate the association between twin growth disorders and HDP. Twin pregnancies resulting in two live births at St George's Hospital between 2000 and 2019 were included. FGR or small-for-gestational-age (SGA) at birth was assessed using singleton and twin reference charts. Intertwin discordance [(large birthweight - small birthweight)/(large birthweight) × 100%)] was calculated. Logistic regression models were performed. SGA (aOR 2.34, 95% CI 1.60-3.44, p < 0.001), intertwin discordance ≥25% (aOR 2.10, 95% CI 1.26-3.49, p = 0.004) and their co-existence (aOR 2.03, 95% CI 1.16-3.54, p = 0.013) were significantly associated with HDP. After adjusting for the known maternal risk factors of HDP and the intertwin discordance, SGA (using the twin charts) was the strongest independent risk factor associated with HDP (aOR 2.12, 95% CI 1.40-3.22, p < 0.001) and preeclampsia (aOR 2.34, 95% CI 1.45-3.76, p < 0.001). This study highlights that the presence of at least one SGA twin is significantly associated with HDP during pregnancy. Therefore, maternal blood pressure should be closely monitored in twin pregnancies complicated by SGA with or without intertwin discordance.

Study on the physical growth status of birthweight discordant twins under 4 years old / 中国实用儿科杂志

OBJECTIVE: To study the physical growth characteristics of birthweight discordant twins(BDT)under 4 years old. METHODS: The physical growth characteristics of BDT under 4 years old born from September 2010 to December 2017 in child health care system of Children's Hospital of Chongqing Medical University were analyzed retrospectively. R 3.5.3 was used to clean up the database,analyze the distribution of different degree of birthweight discordance,and draw the fitting curves. More than 20% of birth weight difference was taken as inclusive criteria of BDT. BDT were divided into preterm or full-term groups,and low birthweight or normal birthweight groups respectively. SPSS 19.0 software was used for statistical analysis. RESULTS: A total of 141 pairs of BDT were included,accounting for 15.4%(141/916). The degree of birthweight difference in premature BDT was higher than that of full-term BDT(t=3.820,P<0.001). The growth discordance of preterm BDT lasted longer. Physical growth of low/very low birthweight BDT was slower than that of normal birthweight BDT under 4 years old. The growth status of BDT didn't reach the average level of WHO growth chart by the time of the last follow-up. CONCLUSION: Birthweight discordance of twins could have longlasting effects on further growth and development. Preterm twins have higher degree of birthweight discordance,and the growth discordance lasts longer. Low birthweight is an important reason for growth retardation of the lighter BDT.Growth of BDT should be monitored regularly to increase follow-up compliance.