Maternal risk factors for the VACTERL association: A EUROCAT case-control study.

BACKGROUND: The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown. OBJECTIVE: To identify maternal risk factors for VACTERL in offspring in a large European study. METHODS: A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). RESULTS: The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4]). CONCLUSION: We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology.

Maternal and perinatal Health Research Collaboration, India (MaatHRI): methodology for establishing a hospital-based research platform in a low and middle income country setting.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India - Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study.

BACKGROUND: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. METHODS: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. RESULTS: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. CONCLUSION: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Epidemiology of partial urorectal septum malformation sequence (or 'persistent cloaca'): a population-based study in seven regions of England and Wales, 1985-2010.

BACKGROUND: Partial urorectal septum malformation (pURSM) sequence (or 'persistent cloaca') is a rare congenital anomaly characterised by a joining of the urethral, anal, and genital openings into a single common channel. This study describes the epidemiology of pURSM sequence in England and Wales including prevalence, additional anomalies, and pregnancy outcomes. METHODS: All cases of pURSM sequence prospectively notified to seven congenital anomaly registers in England and Wales during 1985-2010, whether delivered as live births, spontaneous fetal deaths (≥20 weeks' gestation), or elective terminations of pregnancy for fetal anomaly (TOPFA, any gestation), formed this population-based cohort. The risks of spontaneous fetal and infant death were examined by Kaplan-Meier analysis. Differences in prevalence over time, and between regions, were examined by multilevel Poisson regression. RESULTS: 117 cases were recorded among 4,251,241 total births. Six (5%) pregnancies resulted in spontaneous fetal deaths, 53 (45%) in TOPFA, and 58 (50%) in live births. The prevalence was 2.8 (95% CI 2.3 to 3.4) per 100,000 total births, increasing significantly over time (p=0.002) and differing significantly between regions (p=0.005). 77 cases (66%) had at least one additional major congenital anomaly outside the perineum, including 67 (57%) renal, 29 (25%) musculoskeletal, 26 (23%) digestive system, and 24 (21%) cardiovascular anomalies. The risks of spontaneous fetal and infant death were estimated as 8.9% (95% CI 4.1 to 18.8) and 26.3% (95% CI 15.1 to 43.4) respectively. CONCLUSIONS: This is the largest study of the epidemiology of pURSM sequence. The information will be valuable for families and health professionals whenever a case of pURSM sequence is diagnosed.

Effects of pregnancy planning, fertility, and assisted reproductive treatment on child behavioral problems at 5 and 7 years: evidence from the Millennium Cohort Study.

OBJECTIVE: To examine the effects of pregnancy planning, time to conception (TTC), and assisted reproductive technologies (ART) on child behavior. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 12,380 singletons recruited at 9 months and followed-up at 5 and 7 years. Conceptions were divided into "unplanned" (unplanned, unhappy), "mistimed" (unplanned, happy), "planned" (planned, TTC <12 months), "subfertile" (planned, TTC ≥ 12 months), "ovulation induced" (received clomiphene citrate), and "ART" (IVF or intracytoplasmic sperm injection). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Child behavior (Strengths and Difficulties Questionnaire [SDQ]). RESULT(S): Mistimed and unplanned children had higher average SDQ scores at age 5 and 7 years and were significantly more likely to have a clinically relevant behavioral problem compared with the planned group. The ART children had significantly higher average SDQ scores at both 5 and 7 years compared with the planned group. An increase in clinically relevant behavioral problems was observed at 5 years (odds ratio 2.05 [95% confidence interval 0.96, 4.42]) but failed to reach statistical significance. No effects were observed in the subfertile and ovulation-induced groups. CONCLUSION(S): Unplanned and mistimed children exhibit more behavioral problems than their planned peers. Though ART children have higher mean total difficulties scores, this did not translate into a statistically significant increase in clinically relevant behavioral problems.

Reassured or fobbed off? Perspectives on infertility consultations in primary care: a qualitative study.

BACKGROUND: Infertility affects 9% of couples in the UK. Most couples who visit their GP because they are worried about their fertility will ultimately conceive, but a few will not. Treatment usually happens in secondary care, but GPs can have an invaluable role in starting investigations, referring, and giving support throughout treatment and beyond. AIM: To inform clinical practice by exploring primary care experiences of infertility treatment among females and males, and discussing findings with a reference group of GPs to explore practice experience. DESIGN AND SETTING: A qualitative patient interview and GP focus group study. Interviews were conducted in patients homes in England and Scotland; the focus group was held at a national conference. METHOD: An in-depth interview study was conducted with 27 females and 11 males. A maximum variation sample was sought and interviews were transcribed for thematic analysis. Results were discussed with a focus group of GPs to elicit their views. RESULTS: Feeling that they were being taken seriously was very important to patients. Some felt that their concerns were not taken seriously, or that their GP did not appear to be well informed about infertility. The focus group of GPs highlighted the role of protocols in their management of patients who are infertile, as well as the difficulty GPs faced in communicating both reassurance and engagement. CONCLUSION: Simple things that GPs say and do, such as describing the 'action plan' at the first consultation, could make a real difference to demonstrating that they are taking the fertility problem seriously.

Target decision to delivery intervals for emergency caesarean section based on neonatal outcomes and three year follow-up.

OBJECTIVE: To investigate current target decision to delivery intervals (DDIs) for 'emergency' caesarean section. STUDY DESIGN: Prospective observational cohort study in a teaching hospital providing district and tertiary maternity services delivering 6000 babies per annum. RESULTS: 68% Category 1 deliveries were achieved within 30min and 66% Category 2 within 75min (26% for antepartum Category 2 deliveries). Category 1 deliveries were quicker using general rather than regional anaesthesia (21 vs. 29min, odds ratio [OR] for delivery <30min 4.2, 95%CI 1.3-14.2). 8% Category 1 and 4% Category 2 neonates were acidotic or asphyxiated. The risk of acidosis was not reduced by delivery within 30min for Category 1 (OR 0.56; 0.11-2.81), or within 75min for Category 2 (OR 2.72; 0.6-25.1). Three babies were registered with developmental impairment by three years of age; none were Category 1 deliveries. CONCLUSIONS: Our data suggest that clinical triage is effective, with the more compromised fetus delivered more rapidly using general anaesthesia. For Category 1 deliveries a 30min target DDI is appropriate, although those born after longer DDI did not show developmental impairment. For Category 2 caesarean sections performed for acute fetal distress or concerns, failed instrumental delivery, failure to progress or placental bleeding, a 75min DDI may be an appropriate target but did not protect against acidosis, asphyxia or developmental impairment. Longer DDIs did not result in unfavourable outcomes for other Category 2 indications.