Neurodevelopmental outcome of children with spina bifida aperta repaired prenatally vs postnatally: systematic review and meta-analysis.

OBJECTIVE: To assess the neurodevelopmental outcome of children with spina bifida aperta (SBA) treated prenatally as compared to those treated postnatally. METHODS: We performed a systematic review of the literature in PubMed/MEDLINE, EMBASE, Web of Science and The Cochrane Library, comparing the neurological outcome of infants with SBA treated prenatally vs postnatally. Only randomized controlled trials (RCTs) and non-randomized prospective controlled studies were included. The primary outcome assessed was neurodevelopmental impairment at the age of 1 year or later. Secondary outcomes were preterm birth, need for ventriculoperitoneal (VP) shunt by 12 months of age, absence of signs of hindbrain herniation at the first postnatal magnetic resonance imaging (MRI) evaluation and independent ambulation evaluated at 30 months. RESULTS: Of 11 359 studies identified through the electronic search, six met the inclusion criteria and were assessed in full text and two, one RCT and one prospective cohort study, were ultimately included in the meta-analysis. Sensitivity analysis did not show any difference between the outcomes of the RCT alone and those of the pooled RCT and prospective cohort study. This allowed neurodevelopmental assessment of 213 children between 14 and 53 months of age. Neurodevelopment was assessed by the Bayley Scales of Infant Development II (BSID-II) mental development index corrected for chronological age, with a cut-off of ≥ 70 (representing no more than 2 SD below the mean). The presence of neurodevelopmental impairment was similar between children who underwent prenatal (25/105 (23.8%)) and those who had postnatal (30/108 (27.8%)) repair of SBA (odds ratio (OR), 0.82 (95% CI, 0.43-1.56); P = 0.54), although the risk of prematurity was higher in the prenatal-repair group (OR, 17.62 (95% CI, 7.60-40.87); P < 0.0001). For every two fetuses operated on before birth, there was, compared with those operated on after birth, one additional premature birth (number needed to harm = 2 (95% CI, 1-3)). The need for VP shunt placement by 12 months of age was lower in the prenatal-repair group (45/109 (41.3%)) than in children that had postnatal repair (93/112 (83.0%); OR, 0.14 (95% CI, 0.08-0.26); P < 0.0001). Data on neurodevelopmental impairment in children with a shunt were available only for patients from the prenatal-surgery group of the RCT; in this subgroup, the likelihood for impairment was similar between children who did (7/39 (17.9%)) and those who did not (4/48 (8.3%)) have shunt placement (P = 0.21). At first postnatal MRI evaluation, no signs of hindbrain herniation were detected in 28/88 (31.8%) children who were operated on prenatally compared with 4/89 (4.5%) who had postnatal repair (OR, 9.45 (95% CI, 3.12-28.64); P < 0.0001). Independent ambulation at 30 months was achieved by 41/109 (37.6%) children who underwent prenatal repair compared with 21/111 (18.9%) who had postnatal repair (OR, 2.59 (95% CI, 1.39-4.86); P = 0.003). CONCLUSION: The risk of neurodevelopmental impairment in infants with SBA was similar between those who underwent prenatal and those who had postnatal surgical repair, despite an increased risk of prematurity in the prenatally repaired group. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta-analysis.

OBJECTIVE: There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. METHODS: A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: 'IVF', 'IVF/ICSI', 'ART pregnancy', 'assisted conception', 'birth defect', 'congenital heart defects' and 'congenital malformation or abnormalities'. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. RESULTS: Forty-one studies were identified for review including six case-control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20-1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21-1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03-1.60; P = 0.02; I2 = 0%; P = 0.43). CONCLUSION: Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF/ICSI treatment: meta-analysis of cohort studies.

OBJECTIVE: Preterm birth (PTB) is more common in pregnancies conceived by in-vitro fertilization (IVF) as compared with those conceived naturally. However, the extent to which this is attributed to spontaneous labor or to iatrogenic indications has not been determined. The aim of this study was to quantify the risk of spontaneous PTB (sPTB) in singleton pregnancies resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment as compared with that in spontaneously conceived pregnancies. METHODS: An electronic search of PubMed/MEDLINE, Scopus and Web of Science to September 2017 and manual search of reference lists identified articles comparing the risk of sPTB in IVF/ICSI vs spontaneously conceived singleton pregnancies. Inclusion criteria were singleton conception with IVF/ICSI, PTB defined as delivery before 37 weeks' gestation and cohort design with clear distinction between spontaneous and indicated PTB. The primary outcome was sPTB < 37 weeks. Relevant secondary outcomes were also analyzed, including sPTB < 34 and < 32 weeks, preterm prelabor rupture of membranes, stillbirth, perinatal mortality, neonatal sepsis, respiratory distress syndrome and gastrointestinal morbidity. A meta-analysis provided the estimation of risk of sPTB in IVF/ICSI pregnancies. RESULTS: In total, 674 records were identified from the search, of which 15 met the inclusion criteria and were included in the meta-analysis. A pooled crude analysis of the primary outcome generated a total sample size of 61 677 births, including 8044 singletons conceived after IVF/ICSI and 53 633 conceived spontaneously. A pooled crude data analysis showed a significant increase in the incidence of sPTB < 37 weeks in singleton IVF/ICSI pregnancies compared with those conceived spontaneously (810/8044 (10.1%) vs 2932/53 633 (5.5%); odds ratio (OR), 1.75; 95% CI, 1.50-2.03; I2 = 39%). A subgroup analysis of studies matching for maternal age and parity confirmed the finding (OR, 1.63; 95% CI, 1.30-2.05; I2 = 33%). A pooled crude analysis of secondary outcomes showed a significant increase in the incidence of sPTB < 34 weeks in pregnancies conceived after IVF/ICSI compared with those conceived spontaneously (37/1012 (3.6%) vs 24/1107 (2.2%); OR, 1.78; 95% CI, 1.03-3.08; I2 = 6%) and did not show any significant difference for any of the other secondary outcomes analyzed. The quality of evidence, rated using the GRADE criteria, was low for the outcome sPTB < 37 weeks and very low for sPTB < 34 weeks. CONCLUSIONS: The risk of sPTB in singleton pregnancies resulting from IVF/ICSI is significantly greater than that in spontaneously conceived singletons. These findings should be interpreted with caution given the low quality of the available evidence. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Hypertension negatively affects the pregnancy outcome in patients with antiphospholipid syndrome.

The impact of hypertension in the pregnancies from autoimmune patients is not unequivocally defined. We have prospectively followed 168 pregnancies from 135 patients from four Italian centres to verify the potential impact of hypertension in the antiphospholipid syndrome (APS). The rate of preeclampsia, mean neonatal weight and gestational age at delivery were significantly lower in patients with both APS and hypertension than in patients with hypertension or APS alone. This information may be relevant for counselling and care of these patients.