Gestational length assignment based on last menstrual period, first trimester crown-rump length, ovulation, and implantation timing.

PURPOSE: Understanding the natural length of human pregnancy is central to clinical care. However, variability in the reference methods to assign gestational age (GA) confound our understanding of pregnancy length. Assignation from ultrasound measurement of fetal crown-rump length (CRL) has superseded that based on last menstrual period (LMP). Our aim was to estimate gestational length based on LMP, ultrasound CRL, and implantation that were known, compared to pregnancy duration assigned by day of ovulation. METHODS: Prospective study in 143 women trying to conceive. In 71 ongoing pregnancies, gestational length was estimated from LMP, CRL at 10-14 weeks, ovulation, and implantation day. For each method of GA assignment, the distribution in observed gestational length was derived and both agreement and correlation between the methods determined. RESULTS: Median ovulation and implantation days were 16 and 27, respectively. The gestational length based on LMP, CRL, implantation, and ovulation was similar: 279, 278, 276.5 and 276.5 days, respectively. The distributions for observed gestational length were widest where GA was assigned from CRL and LMP and narrowest when assigned from implantation and ovulation day. The strongest correlation for gestational length assessment was between ovulation and implantation (r = 0.98) and weakest between CRL and LMP (r = 0.88). CONCLUSIONS: The most accurate method of predicting gestational length is ovulation day, and this agrees closely with implantation day. Prediction of gestational length from CRL and known LMP are both inferior to ovulation and implantation day. This information could have important implications on the routine assignment of gestational age.

S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia.

AIMS: To determine the effects of in vivo S-nitrosoglutathione (GSNO) infusion on cardiovascular function, platelet function, proteinuria and biomarker parameters in early-onset pre-eclampsia. METHODS: We performed an open-label dose-ranging study of GSNO in early-onset pre-eclampsia. Six women underwent GSNO infusion whilst receiving standard therapy. The dose of GSNO was increased incrementally to 100 µg min(-1) whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternal-fetal Doppler parameters were measured at each dose. Platelet P-selectin, protein-to-creatinine ratio and soluble anti-angiogenic factors were measured pre- and postinfusion. RESULTS: Augmentation index fell at 30 µg min(-1) S-nitrosoglutathione (-6%, 95% confidence interval 0.6 to 13%), a dose that did not affect blood pressure. Platelet P-selectin expression was reduced [mean (interquartile range), 6.3 (4.9-7.6) vs. 4.1 (3.1-5.7)% positive, P = 0.03]. Soluble endoglin levels showed borderline reduction (P = 0.06). There was a borderline significant change in pre-to-postinfusion protein-to-creatinine ratio [mean (interquartile range), 0.37 (0.09-0.82) vs. 0.23 (0.07-0.49) g mmol(-1) , P = 0.06]. Maternal uterine and fetal Doppler pulsatility indices were unchanged. CONCLUSIONS: In early-onset pre-eclampsia, GSNO reduces augmentation index, a biomarker of small vessel tone and pulse wave reflection, prior to affecting blood pressure. Proteinuria and platelet activation are improved at doses that affect blood pressure minimally. These effects of GSNO may be of therapeutic potential in pre-eclampsia, a condition for which no specific treatment exists. Clinical studies of GSNO in early-onset pre-eclampsia will determine whether these findings translate to improvement in maternal and/or fetal outcome.

Association Between Prepregnancy Cardiovascular Function and Subsequent Preeclampsia or Fetal Growth Restriction.

Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; P=0.002) and cardiac index (2.9 versus 3.3 L/min per meter2; P=0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; P=0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm-5; P<0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.

A longitudinal study of maternal cardiovascular function from preconception to the postpartum period.

OBJECTIVE: Our objective was to investigate the extent of changes in maternal cardiovascular function, lipids and renal function during normal pregnancy from preconception to postpartum period. METHODS: In this prospective study of 54 normal pregnancies, detailed hemodynamics were performed preconception, at 6, 23 and 33 weeks during pregnancy and 16 weeks postpartum. RESULTS: Although the greatest reduction of blood pressures (BPs) and augmentation index occurred in early pregnancy (Δbrachial systolic: 4 ±â€Š7  mmHg, Δcentral systolic: 7 ±â€Š7  mmHg; P < 0.001), the peripheral vascular resistance reached a nadir (Δ: 222 ±â€Š215 dynes.s.cm; P < 0.001) by the second trimester. The greatest increase in cardiac output occurred by the second trimester (Δ: 0.6 ±â€Š1 l/min, P < 0.001), whereas the heart rate increased maximally by the third trimester (Δ: 13 ±â€Š11  bpm; P = 0.001). The unadjusted aortic pulse wave velocity decreased in the second trimester (P < 0.001), however, when adjusted for mean arterial pressure this was not significant (P = 0.06). BPs were lower (Δ brachial systolic: 5 ±â€Š8  mmHg; P < 0.001) and augmentation index higher (Δ: 2.5 ±â€Š7%; P = 0.01) postpartum than preconception. The cholesterol:high-density lipoprotein ratio, serum low density lipoprotein and serum creatinine all fell (P < 0.001) in the first trimester. CONCLUSION: We have shown that normal pregnancy, irrespective of parity, is associated with significant changes commencing very early in pregnancy, continuing throughout pregnancy, and some of these changes persisted postpartum. Therefore, first trimester or postpartum baselines will underestimate the true extent of pregnancy-related changes. Prospective studies of cardiovascular function from preconception to postpartum will provide more reliable estimates of the influence of cardiovascular maladaptation during pregnancy complications and their effect on longer term cardiovascular function.

Cardiovascular disease in menopause: does the obstetric history have any bearing?

Cardiovascular disease remains a leading cause of morbidity and mortality in menopausal women in spite of the overall reduction in age-adjusted mortality from the disease in the last few years. It is now clear that mechanisms of cardiovascular disease in menopausal women are similar to men and rather than midlife acceleration of cardiovascular disease in women, the final impact of cardiovascular disease in later life may be a reflection of cardiovascular changes during reproductive years as a result of woman's obstetric history. A decade after the Women's Health Initiative trial, there is upcoming evidence to suggest that hormone replacement therapy in young recently menopausal women has a cardioprotective effect. Cardiovascular changes during normal pregnancy or pregnancy complications such as preeclampsia may affect a woman's long-term cardiovascular health. Therefore, it is plausible that the cardioprotective benefit of hormone replacement therapy depends on occult pre-existing cardiovascular risks in women in relation to their previous obstetric history. In this review, we describe the cardiovascular changes during and after pregnancy in obstetric complications such as recurrent miscarriage, preeclampsia, intrauterine growth restriction, preterm labour and gestational diabetes; existing evidence regarding their association with cardiovascular disease later in life, and hypothesize possible mechanisms. Our aim is to improve the understanding and highlight the importance of including obstetric history in risk assessment in menopausal women and individualizing their risks before prescribing hormone replacement therapy. Future research in risk benefit assessment of hormone replacement therapy should also account for a woman's background cardiovascular risk in the light of her obstetric history.

Cardiovascular function in women with recurrent miscarriage, pre-eclampsia and/or intrauterine growth restriction.

OBJECTIVE: To investigate prepregnancy cardiovascular function and risk factors in women with previous pregnancy complications. METHODS: Thirty-four women with previous normal pregnancy (controls), 26 with unexplained recurrent miscarriage (RM) and 14 with pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR), planning to conceive were recruited. Brachial and central blood pressures (BP), cardiac output (CO), peripheral vascular resistance (PVR), aortic stiffness, blood biochemistry and platelet aggregation were assessed. RESULTS: Women with previous PE/IUGR had higher brachial diastolic BP (78 ± 9 vs 71 ± 7 mmHg; p = 0.03), central systolic BP (107 ± 10 vs 99 ± 8 mmHg; p = 0.03), mean arterial pressure (92 ± 10 vs 84 ± 8 mmHg; p = 0.01) and PVR (1499 ± 300 vs 1250 ± 220 dynes.s(-1) cm(-5); p = 0.005), than the controls. No differences were observed in either cardiovascular function or blood biochemistry in women with unexplained RM compared with the controls. Women with previous PE/IUGR though not with RM had a stronger family history of cardiovascular disease (CVD) than controls. CONCLUSIONS: Women with previous PE and/or IUGR had higher BP and PVR compared with controls, which may predispose them to CVD later in life. However, in the absence of underlying vascular pathology, women with unexplained RM did not have abnormal cardiovascular function. Prepregnancy period provides an opportunity to identify cardiovascular risks in relation to previous obstetric history.

Mid-trimester maternal heart rate is related to neonatal birth weight.

OBJECTIVE(S): We sought to establish the relationship between maternal mid-trimester heart rate (HR) and neonatal birth weight in women at high a priori risk of preeclampsia. STUDY DESIGN: Ninety-nine women were recruited following second trimester uterine artery Doppler assessment. Maternal blood pressure (BP) and HR were measured between 23(+4) and 30(+5) weeks gestation and neonatal birth weight was expressed as a z-score. The relationship between the parameters was investigated using Pearson's correlation coefficient. RESULTS: There was a significant positive correlation between maternal HR and neonatal birth weight z-score, r = 0.22 (95% CI: 0.02-0.40), p = 0.03. An inverse correlation was found between uterine artery Doppler pulsatility index (PI) and maternal HR, r = -0.43 (95% CI: 0.01-0.40), p = 0.0001, and neonatal birth weight, r = -0.3 (95% CI: -0.47 to -0.10), p = 0.004. For neonatal birth weight z-score <-1.65, r = 0.69 (95% CI: 0.15-0.91), p = 0.02. There was no relationship between BP and uterine artery Doppler or neonatal birth weight. CONCLUSION: The finding of a continuous relationship between maternal HR and neonatal birth weight prior to the onset of fetal growth restriction is novel, suggesting that maternal cardiovascular adaptation is reflected by neonatal birth weight. Lower maternal HR is associated with lower neonatal birth weight and vice versa. Further, we confirm the reported associations between uterine artery Doppler PI and both maternal HR and neonatal birth weight.

The feasibility of prospectively studying maternal cardiovascular changes from before conception.

There is compelling evidence that factors before pregnancy and around implantation may have a bearing on maternal cardiovascular adaptation to pregnancy and subsequent pregnancy outcome. Prospective studies from before pregnancy are associated with difficulties in recruitment, low conception rates, early pregnancy loss and low retention of participants during pregnancy and postpartum follow-up. The objective of this study was to establish the feasibility of recruiting to; conducting and completing a prospective cohort study from before pregnancy to the postpartum period. One-hundred and forty-three women planning to conceive were recruited. They underwent detailed cardiovascular measurements including brachial and central blood pressures, cardiac output, aortic stiffness and pulse wave reflection, metabolic function and platelet aggregation. Once pregnant, the cardiovascular assessments were repeated at intervals throughout pregnancy and postpartum. Of 143 women, 101 women conceived within 18 months. Seventy-one had viable pregnancies at 10-14 weeks. Among the 70 live-births, three women developed preeclampsia (PE) and two had intrauterine growth restriction. Two were lost to follow-up. It is feasible to recruit women who are planning to conceive, conduct prepregnancy cardiovascular assessments and follow them up during pregnancy. Based on the current data, approximately half the women recruited will have healthy ongoing pregnancies. This information would allow the design of a study, powered for pregnancy complications such as PE, to enable investigation of the 'cause and effect' relationship between abnormal cardiovascular function and pregnancy complications.

Maternal cardiovascular changes from pre-pregnancy to very early pregnancy.

OBJECTIVE: Our aim was to assess changes in maternal cardiovascular haemodynamics, including central blood pressure (BP), wave reflections and aortic stiffness, from pre-pregnancy to very early pregnancy. METHODS: Fifty-six healthy nulliparous or women with previous uncomplicated pregnancy were studied prior to conception and in very early pregnancy. Assessments of brachial and central BPs, pulse wave reflection quantified by augmentation index (AIx), aortic stiffness using carotid femoral pulse wave velocity (aPWV) and cardiac output (CO) were performed. RESULTS: Pregnancy measurements were obtained at median gestational age of 6.3 weeks [interquartile range (IQR) 6-6.5 weeks] from the last menstrual period. Whilst heart rate (HR) increased from 67  ±â€Š 10 to 71  ±  10  bpm. (P  =  0.001), brachial SBP, DBP and central SBP were all lower than the pre-pregnancy values (109  ±â€Š 10 to 104  ±â€Š 7 mmHg, 72  ±  8 to 65  ±  6 mmHg and 99  ±â€Š 10 to 92  ±â€Š 7 mmHg, respectively; P  <  0.001 for all). AIx adjusted for HR fell (19  ±â€Š 10 to 13  ±â€Š 9%; P  =  0.001) as did peripheral vascular resistance (PVR; 1234 ±â€Š229 to 1128  ±  280 dynes/s/cm; P = 0.003). aPWV adjusted for mean arterial pressure (MAP) was unchanged (5.3  ±â€Š 0.6 to 5.1  ±  0.6m/s; P  =  0.2). CONCLUSION: Significant changes occur in brachial and central BP, AIx and PVR in successful, ongoing pregnancies, by about 6-7 weeks gestation; much earlier than has hitherto been assumed. Using late first trimester data as 'baseline' cannot be relied on to estimate the extent of cardiovascular changes in normal pregnancy. Future studies of cardiovascular changes in pregnancy should, therefore, have a pre-pregnancy starting point.

Is intrapartum fetal blood sampling a gold standard diagnostic tool for fetal distress?

Developed in 1960s, cardiotocography is a screening test and fetal blood sampling (FBS) is an adjunctive, diagnostic technique to detect fetal hypoxia. A fetal blood sample pH value of less than 7.20 has a higher specificity than a pathological CTG to predict low Apgar score at 1 min. Though with a pathological CTG and despite a normal FBS pH value the risk of delivering a hypoxic infant is 30-50%, FBS has assumed considerable importance in purportedly reducing unnecessary obstetric intervention. The evidence for this is weak: the use of FBS with CTG has been shown to reduce operative vaginal deliveries though not Caesarean sections due to fetal distress. There is no difference in the umbilical artery pH at delivery with the use of intermittent FBS with CTG compared to CTG alone. FBS is an invasive procedure: obtaining an adequate blood sample is often difficult and the pH results are affected by handling of the sample, aerobic contamination and processing. Validation of intrapartum FBS requires that the pH and other values obtained are compared to a 'gold standard' technique. Although FBS has been compared to other tests such as scalp lactate, pulse oximetry, fetal ECG waveform analysis, and central haemodynamics in labouring rhesus monkeys, none of these can be considered as 'gold standard'. In the light of the existing evidence, the role of intrapartum FBS as a gold standard diagnostic technique is unproven.