Vitamin D status and requirements during pregnancy and lactation

Vitamin D deficiency during pregnancy, lactation, and early infancy has been widely reported. Current understanding of vitamin D metabolism during pregnancy and lactation is incomplete, and to date, experimental data to support vitamin D requirements for these life stages are scarce. There is a shortage of nationally representative data and appropriate reference ranges for serum 25-hydroxyvitamin D (25OHD) during pregnancy, lactation and infancy, including in umbilical cord blood. This thesis described concentrations of total 25OHD and individual metabolites including 25OHD3, 25OHD2, and 3-epi-25OHD3 at 15 weeks’ gestation in a large seasonally balanced pregnancy cohort study (n 1768), carried out in Cork, Ireland (52oN). The prevalence of low 25OHD concentrations in pregnant women was higher than published reports in other Caucasian women, and was highest among non-users of vitamin D-containing supplements during winter. A longitudinal pregnancy study was included which suggested gestational stages had an impact on the total serum 25OHD concentration. This thesis incorporated a randomized controlled trial carried out among 100 women across 3 intervention groups using 20 μg/day of vitamin D3 with or without 500 mg calcium, or placebo, over 12-weeks of lactation to investigate the vitamin D requirement for lactating mothers and the vitamin D content of human milk. A daily intake of 25 μg/day was suggested to meet the requirement of lactating women to maintain a 25OHD levels above 50 nmol/L in 97.5% of the population at 52oN all year around. However, vitamin D content in human milk did not increase in response to supplementation. Serum 25OHD concentration has been used as a predictor of a number of health outcomes. This thesis reported large differences in serum 25OHD concentrations using different methods in 86 umbilical cord samples. The need for international standardization of serum 25OHD measurements was re-emphasized in this thesis.

Surveillance during pregnancy: methods and response rates from a hospital based pilot study of the Pregnancy Risk Assessment Monitoring System in Ireland

Background: Many European countries including Ireland lack high quality, on-going, population based estimates of maternal behaviours and experiences during pregnancy. PRAMS is a CDC surveillance program which was established in the United States in 1987 to generate high quality, population based data to reduce infant mortality rates and improve maternal and infant health. PRAMS is the only on-going population based surveillance system of maternal behaviours and experiences that occur before, during and after pregnancy worldwide.Methods: The objective of this study was to adapt, test and evaluate a modified CDC PRAMS methodology in Ireland. The birth certificate file which is the standard approach to sampling for PRAMS in the United States was not available for the PRAMS Ireland study. Consequently, delivery record books for the period between 3 and 5 months before the study start date at a large urban obstetric hospital [8,900 births per year] were used to randomly sample 124 women. Name, address, maternal age, infant sex, gestational age at delivery, delivery method, APGAR score and birth weight were manually extracted from records. Stillbirths and early neonatal deaths were excluded using APGAR scores and hospital records. Women were sent a letter of invitation to participate including option to opt out, followed by a modified PRAMS survey, a reminder letter and a final survey.Results: The response rate for the pilot was 67%. Two per cent of women refused the survey, 7% opted out of the study and 24% did not respond. Survey items were at least 88% complete for all 82 respondents. Prevalence estimates of socially undesirable behaviours such as alcohol consumption during pregnancy were high [>50%] and comparable with international estimates.Conclusion: PRAMS is a feasible and valid method of collecting information on maternal experiences and behaviours during pregnancy in Ireland. PRAMS may offer a potential solution to data deficits in maternal health behaviour indicators in Ireland with further work. This study is important to researchers in Europe and elsewhere who may be interested in new ways of tailoring an established CDC methodology to their unique settings to resolve data deficits in maternal health.

The Protection of Life During Pregnancy Act 2013: Suicide, dignity and the Irish discourse on abortion

Accepted Version

The effect of positive psychological interventions on psychological and physical well-being during pregnancy

Prenatal well-being can have significant effects on the mother and developing foetus. Positive psychological interventions, including gratitude and mindfulness, consistently demonstrate benefits for well-being in diverse populations. No research has been conducted on gratitude during pregnancy; the few studies of prenatal mindfulness interventions have demonstrated well-being benefits. The current study examined the effects of gratitude and mindfulness interventions on prenatal maternal well-being, cortisol and birth outcomes. Five studies were conducted. Study 1 was a systematic review of mindfulness intervention effects on cortisol; this highlighted potential benefits of mindfulness but the need for rigorous protocols in future research. In Study 2 a gratitude and a mindfulness intervention were developed and evaluated; findings indicate usefulness of two 3 week interventions. Study 3 examined the effects of these interventions in a randomised controlled trial (RCT) of non-pregnant women, before examining a pregnant group. No significant intervention effects were found in this study, potentially due to insufficient power and poor protocol adherence. Changes in expected directions were observed for most outcomes and the potential utility of a combined gratitude and mindfulness intervention was noted. In Study 4 a gratitude during pregnancy (GDP) scale was developed and the reliability of an existing mindfulness measure (MAAS) was examined in a pregnant group. Both scales were found to be suitable and reliable measures in pregnancy. Study 5 incorporated the findings of the previous four studies to examine of the effect of a combined mindfulness and gratitude intervention with a group of pregnant women. Forty-six participants took part in a 5-week RCT that examined intervention effects on prenatal gratitude, mindfulness, happiness, satisfaction with life, social support, prenatal stress, depression and sleep. Findings indicated that the intervention improved sleep quality and that effects for prenatal distress were approaching significance. Issues of attrition and non-compliance to study protocols were problematic and are discussed. In summary, the current thesis highlights the need for robust measurement, and intervention and cortisol sampling protocols in future research, particularly with pregnant groups. Findings also demonstrate tentative benefits of a gratitude and mindfulness intervention during pregnancy.

The effect of moderate gestational alcohol consumption during pregnancy on speech and language outcomes in children: a systematic review

Consensus has not been reached on safe alcohol consumption recommendations during pregnancy. The National Institutes for Care and Health Excellence (NICE) in the UK suggest that one to two drinks not more than twice per week is safe. However, the speech and language effects of even low levels of alcohol use among offspring are unknown. The aim of this study was to review systematically the evidence on studies of the effect of low to moderate levels of alcohol consumption during pregnancy (up to 70 grams of alcohol per week) compared to abstinence on speech and language outcomes in children.

Monitoring behaviours and experiences before, during and after pregnancy in Ireland

Background: On-going surveillance of behaviours during pregnancy is an important but overlooked population health activity that is particularly lacking in Ireland. Few, if any, nationally representative estimates of most maternal behaviours and experiences are available. While on-going surveillance of maternal behaviours has not been a priority thus far in European countries including Ireland, on-going surveillance was identified as a key priority in the United States (US) during the 1980’s when the Pregnancy Risk Assessment Monitoring System (PRAMS), was established. Today, PRAMS is the only surveillance programme of maternal behaviours and experiences world-wide. Although on-going prevalence estimates are required in Ireland, studies which examine the offspring health effects of maternal behaviours are also required, since various questions regarding maternal exposures and their offspring health effects remain unanswered. Gestational alcohol consumption is one such important maternal exposure which is common in pregnancy, though its offspring health effects are unclear, particularly at lower or moderate levels. Thus, guidelines internationally have not reached consensus on safe alcohol recommendations for pregnant women. The aims of this thesis are to implement the PRAMS in Ireland (PRAMS Ireland), to describe the prevalence of health behaviours around the time of pregnancy in Ireland and to examine the effect of health behaviours on pregnancy and child outcomes (specifically the relationship between alcohol use during pregnancy and infant and child growth). Structure: In Chapter 1, a brief background and rationale for the work, as well as the thesis aims and objective is provided. A detailed description of the design and implementation of PRAMS Ireland is described in Chapter 2. Chapter 3 and Chapter 4 describe the methodological results of the implementation of the PRAMS Ireland pilot study and PRAMS Ireland main study. In Chapter 5, a comparison of alcohol prevalence in two Irish studies (PRAMS Ireland and Growing up in Ireland (GUI)) and one multi-centre prospective cohort study, Screening for Pregnancy Endpoints (SCOPE) Study is detailed. Chapter 6 describes findings on adherence to National Clinical Guidelines on health behaviours and nutrition around the time of pregnancy in PRAMS Ireland. Findings on exposure to alcohol use in pregnancy and infant growth outcomes are described in Chapter 7 and Chapter 8. The results of analysis conducted to examine the impact of gestational alcohol use on offspring growth trajectories to age ten are described in Chapter 9. Finally, a discussion of the findings, strengths and limitations of the thesis, direction for future research, policy, practice and public health implications are discussed in Chapter 10.Results: Implementation of PRAMS: PRAMS may be an effective system for the surveillance of health behaviours around the time of pregnancy in the Irish context. PRAMS Ireland had high response rates (67% and 61% response rates in the pilot and main study respectively), high item completion rates and valid prevalence estimates for many health behaviours. Examining prevalence of health behaviours: We found high levels of alcohol consumption before and during pregnancy, poor adherence to healthy diets and high levels of smoking before and during pregnancy among women in Ireland. Socially disadvantaged women had higher rates of deleterious health behaviours before pregnancy, although women with the most deleterious behaviour profiles before pregnancy appeared to experience the greatest gain in protective health behaviours during pregnancy. The impact of alcohol use on infant and offspring growth: We found that low and moderate levels of alcohol use did not impact on birth outcomes or offspring growth whereas heavy alcohol consumption resulted in reduced birth length and birth weight; however, this finding was not consistently observed across all studies. Selection, reporting and confounding biases which are common in observational research could be masking harmful effects. Conclusion: PRAMS is a valid and feasible method of surveillance of health behaviours around the time of pregnancy in Ireland. A surveillance program of maternal behaviours and experiences is immediately warranted due to high levels of deleterious health behaviours around the time of pregnancy in Ireland. Although our results do not indicate any evidence of harm, given the quality of evidence available, abstinence and advice of abstinence from alcohol may be the most prudent choice for patients and healthcare professionals respectively. Further studies of the effects of gestational alcohol use are required; particularly those which can reduce selection bias, reporting bias and confounding.

Prediction and prevention of venous thrombosis in pregnancy

Venous thromboembolism (VTE) remains the leading cause of maternal mortality. Reports identified further research is required in obese and women post caesarean section (CS). Risk factors for VTE during pregnancy are periodically absent indicating the need for a simple and effective screening tool for pregnancy. Perturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications. This thesis had 4 main aims: 1) To investigate anticoagulant effects following a fixed thromboprophylaxis dose in healthy women post elective CS. 2) To evaluate the calibrated automated thrombogram (CAT) assay as a potential predictive tool for thrombosis in pregnancy. 3) To compare the anticoagulant effects of fixed versus weight adjusted thromboprophylaxis dose in morbidly obese pregnant women. 4) To investigate the LMWH effects on human haemostatic gene and antigen expression in placentae and plasma from the uteroplacental , maternal and fetal circulation. Tissue factor pathway inhibitor (TFPI), thrombin antithrombin (TAT), CAT and anti-Xa levels were analysed. Real-time PCR and ELISA were used to quantify mRNA and protein expression of TFPI and TF in placental tissue. In women post CS, anti-Xa levels do not reflect the full anticoagulant effects of LMWH. LMWH thromboprophylaxis in this healthy cohort of patients appears to have a sustained effect in reducing excess thrombin production post elective CS. The results of this study suggest that predicting VTE in pregnant women using CAT assay is not possible at present time. The prothrombotic state in pregnant morbidly obese women was substantially attenuated by weight adjusted but not at fixed LMWH doses. LMWH may be effective in reducing in- vivo thrombin production in the uteroplacental circulation of thrombophilic women. All these results collectively suggest that at appropriate dosage, LMWH is effective in attenuating excess thrombin generation, in low risk pregnant women post caesarean section or moderate to high risk pregnant women who are morbidly obese or tested positive for thrombophilia. The results of the studies provided data to inform evidence-based practice to improve the outcome for pregnant women at risk of thrombosis.