Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Do parental heights influence pregnancy length?: A population-based prospective study, HUNT 2.

BACKGROUND: The objective of this study was to examine the association of maternal and paternal height with pregnancy length, and with the risk of pre- and post-term birth. In addition we aimed to study whether cardiovascular risk factors could explain possible associations. METHODS: Parents who participated in the Nord-Trøndelag Health Study (HUNT 2; 1995-1997) were linked to offspring data from the Medical Birth Registry of Norway (1997-2005). The main analyses included 3497 women who had delivered 5010 children, and 2005 men who had fathered 2798 pregnancies. All births took place after parental participation in HUNT 2. Linear regression was used to estimate crude and adjusted differences in pregnancy length according to parental heights. Logistic regression was used to estimate crude and adjusted associations of parental heights with the risk of pre- and post-term births. RESULTS: We found a gradual increase in pregnancy length by increasing maternal height, and the association was essentially unchanged after adjustment for maternal cardiovascular risk factors, parental age, offspring sex, parity, and socioeconomic measures. When estimated date of delivery was based on ultrasound, the difference between mothers in the lower height quintile (<163 cm cm) and mothers in the upper height quintile (≥ 173 cm) was 4.3 days, and when estimated date of delivery was based on last menstrual period (LMP), the difference was 2.8 days. Shorter women (< 163 cm) had lower risk of post-term births, and when estimated date of delivery was based on ultrasound they also had higher risk of pre-term births. Paternal height was not associated with pregnancy length, or with the risks of pre- and post-term births. CONCLUSIONS: Women with shorter stature had shorter pregnancy length and lower risk of post-term births than taller women, and when EDD was based on ultrasound, they also had higher risk of preterm births. The effect of maternal height was generally stronger when pregnancy length was based on second trimester ultrasound compared to last menstrual period. The association of maternal height with pregnancy length could not be explained by cardiovascular risk factors. Paternal height was neither associated with pregnancy length nor with the risk of pre- and post-term birth.

Offspring birth weight and cardiovascular risk in parents: a population-based HUNT 2 study.

Low birth weight is associated with increased risk of cardiovascular disease and type 2 diabetes in later life. The fetal insulin hypothesis suggests that shared genetic factors partly explain this association. If fetal genes predispose to both low birth weight and cardiovascular disease in adulthood, fathers of offspring with low birth weight should display an unfavorable profile of cardiovascular risk factors. To study this, the authors linked data on more than 14,000 parents, collected from the second Health Study of Nord Trøndelag County, Norway (HUNT 2, 1995-1997), to offspring data from the Norwegian Medical Birth Registry (1967-2005). Linear regression was used to study associations of offspring birth weight for gestational age with the parents' body mass index, waist circumference, blood pressure, glucose, and serum lipids. All analyses were adjusted for shared environment by means of the socioeconomic measures, lifestyle, and cardiovascular risk factors of the partner. The authors found that low offspring birth weight for gestational age was associated with increased paternal blood pressure, body mass index, waist circumference, and unfavorable levels of glucose and lipids. For mothers, associations similar to those for fathers were found for blood pressure, whereas associations in the opposite direction were found for glucose, lipids, and body mass index. The paternal findings strengthen the genetic hypothesis.

Cardiovascular risk factors prior to conception and the length of pregnancy: population-based cohort study.

OBJECTIVE: To study the association of prepregnancy blood pressure, lipids, and glucose with length of pregnancy, and to assess whether the association between preterm delivery and later maternal cardiovascular disease may be due to common risk factors. STUDY DESIGN: Prospective study linking information of 3506 women in the HUNT Study with 4990 singleton births recorded in the Medical Birth Registry of Norway. RESULTS: Unfavorable prepregnancy levels of triglycerides, cholesterol, high-density lipoprotein-cholesterol, and glucose were associated with increased risk of preterm birth and shorter gestational length. Triglycerides above 1.6 mmol/L were associated with 60% higher risk of preterm birth (odds ratio, 1.6, 95% confidence interval, 1.0-2.5), compared with triglycerides below 0.7 mmol/L. Blood pressure was positively associated with risk of preterm birth and shorter gestational length, but these associations were substantially attenuated after adjustment for hypertensive disorders in pregnancy. CONCLUSION: Women with unfavorable cardiovascular risk factors before conception have excess risk of preterm birth.

Hypertensive disorders in pregnancy and paternal cardiovascular risk: a population-based study.

PURPOSE: It has been suggested that paternal genes may contribute to the risk of maternal hypertensive disorders in pregnancy and that genes associated with cardiovascular disease could be involved in the etiology of maternal hypertensive disorders in pregnancy. If these genes are of fetal origin, one would expect that paternal cardiovascular risk factors are associated with the fathering of pregnancies in which the mothers experience hypertensive disorders. Thus, we have studied 14,130 offspring and parents in Norway (1967-1997) to assess whether the fathering of pregnancies complicated by hypertensive disorders in the mother is associated with paternal cardiovascular risk factors. METHODS: In a population-based study of 14,130 family units, data on parental cardiovascular risk factors (blood pressure, body mass index, waist circumference, nonfasting serum lipids and glucose) collected in the Norwegian Hunt Study (1995-1997) were linked to pregnancy data from the Medical Birth Registry of Norway (1967-1997). Multiple linear regression methods were used, and all analyses were adjusted for lifestyle factors likely to be shared by the parents. RESULTS: There was no association between hypertensive disorders in pregnancy and paternal cardiovascular risk factors. CONCLUSIONS: We found no evidence that the fathering of pregnancies complicated by hypertensive disorders in the mother is associated with an unfavorable paternal cardiovascular risk profile.

Changes in genital anatomy and microbiology in girls between age 6 and age 12 years: a longitudinal study.

STUDY OBJECTIVE: To study changes in genital anatomy and occurrence of human papillomavirus and Gardnerella vaginalis in girls resulting from growth and development. DESIGN: At age 11-12 years, an invitation was sent to 180 girls to attend a follow-up examination. All girls had previously participated in a study exploring anogenital anatomy and microbiology in children selected for non-abuse at age 5 and 6. The genital area was examined with a colposcope and microbiological samples for Gardnerella vaginalis (GV) and human papillomavirus (HPV) were collected. GV was identified by conventional criteria and HPV by a PCR method. RESULTS: Thirty-one girls were examined twice, at mean age 5.7 and 12.0 years. At first examination all were pre-pubertal. At second examination 21 girls were B2/P2 or above. Significantly more girls had developed a structure called a fossa groove. A thick and redundant hymen with a tendency of folding outward was more common at the second examination. Two girls had GV and one girl had HPV-16 identified. Another girl was classified to have a deep notch and a probable transection in her hymen, and this girl reported a painful insertion of a tampon. All girls denied sexual activity. CONCLUSION: The main genital finding in girls entering puberty is the hymen becoming thick and redundant with a tendency of folding out. In the study findings associated with sexual activity were discovered in two girls, and the possibility of alternative explanations is discussed.