Ophthalmic artery Doppler at 19-23 weeks' gestation in pregnancies that deliver small-for-gestational-age neonates.

OBJECTIVES: First, to explore hemodynamic differences between pregnancies delivering a small-for-gestational-age (SGA) neonate in the absence of hypertensive disorders and those that develop pre-eclampsia (PE) or gestational hypertension (GH), by comparing the ophthalmic artery peak systolic velocity (PSV) ratio and first (PSV1) and second (PSV2) PSV at 19-23 weeks' gestation, and second, to compare these pregnancies for markers of placental perfusion and function. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for assessment of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, PSV1, PSV2, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). The values of PSV ratio, PSV1, PSV2, MAP, UtA-PI and PlGF were converted to multiples of the median (MoM) or deltas. Mean MoMs or deltas of these biomarkers in the SGA, PE and GH groups were compared with those in the unaffected group. The definition of SGA was birth weight below the 10th percentile in the absence of PE or GH. RESULTS: The study population of 5214 pregnancies contained 4375 (83.9%) that were unaffected by SGA, PE or GH, 563 (10.8%) complicated by SGA, 157 (3.0%) with PE and 119 (2.3%) with GH. There were three main findings of the study. First, in the SGA, PE and GH groups, compared with unaffected pregnancies, the PSV ratio delta, PSV2 MoM, MAP MoM and UtA-PI MoM were increased and PlGF MoM was decreased; however, the magnitude of most changes was smaller in the SGA group than in PE and GH groups. Second, in the PE and GH groups, but not in the SGA group, PSV1 MoM was increased. Third, in general, in the pathological pregnancies, the magnitude of deviation of biomarkers from unaffected pregnancies was greater for those delivering at < 37 than at ≥ 37 weeks' gestation. CONCLUSION: In mid-gestation, pregnancies that subsequently develop hypertensive disorders and those delivering a SGA neonate, compared with unaffected pregnancies, have abnormal uteroplacental measurements and increased maternal ophthalmic artery PSV ratio. These data suggest similar pathophysiology in the two conditions, with evidence of placental dysfunction and increased peripheral vascular resistance, but the magnitude of abnormalities is greater in hypertensive disorders. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler at 35-37 weeks' gestation in pregnancies with small or growth-restricted fetuses.

OBJECTIVES: First, to compare the ophthalmic artery peak systolic velocity (PSV) ratio at 35-37 weeks' gestation among women who delivered small-for-gestational-age (SGA) or growth-restricted (FGR) neonates in the absence of hypertensive disorders, women who developed pre-eclampsia (PE) or gestational hypertension (GH) and those without SGA, FGR, PE or GH. Second, to examine the association of PSV ratio with placental growth factor (PlGF) and mean arterial pressure (MAP). Third, to assess the associations of PSV ratio, PlGF and MAP with birth-weight Z-score and percentile. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, first (PSV1) and second (PSV2) peaks of systolic velocity, MAP and serum PlGF. The values of PSV ratio, MAP and PlGF were converted to multiples of the median (MoM) or delta values, and the median MoM or delta of these variables in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, PlGF MoM and MAP MoM with birth-weight Z-score after exclusion of PE and GH cases. Regression analysis was also used to examine the association of PSV ratio delta with log10 PlGF MoM and log10 MAP MoM. RESULTS: The study population included 2287 pregnancies, of which 1954 (85.4%) were not affected by FGR, SGA, PE or GH, 49 (2.1%) were complicated by FGR in the absence of PE or GH, 160 (7.0%) had SGA in the absence of FGR, PE or GH, 60 (2.6%) had PE and 64 (2.8%) had GH. Compared with unaffected pregnancies, in both the FGR and SGA groups, the means of PSV ratio delta (0.042 (95% CI, 0.007-0.076) and 0.032 (95% CI, 0.016-0.049), respectively) and MAP MoM (1.028 (95% CI, 1.006-1.050) and 1.048 (95% CI, 1.035-1.060), respectively) were increased, while the mean of PlGF MoM was decreased (0.495 (95% CI, 0.393-0.622) and 0.648 (95% CI, 0.562-0.747), respectively). However, the magnitude of these changes was smaller than in the PE and GH groups. Ophthalmic artery waveform analysis revealed that the predominant feature of pregnancies complicated by SGA in the absence of hypertensive disorders was a reduction in PSV1, whereas, in those with hypertensive disorders, there was an increase in PSV2. In non-hypertensive pregnancies, there were linear inverse associations of PSV ratio delta and MAP MoM with birth-weight Z-score, with increased values in small neonates and decreased values in large neonates. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small neonates and high PlGF levels in large neonates. There was a significant correlation of ophthalmic artery PSV ratio delta with both log10 MAP MoM (0.124 (95% CI, 0.069-0.178)) and log10 PlGF MoM (-0.238 (95% CI, -0.289 to -0.185)). CONCLUSION: Assuming that the ophthalmic artery PSV ratio is a reflection of the interplay between cardiac output and peripheral vascular resistance, the linear association between PSV ratio and birth-weight Z-score in non-hypertensive pregnancies suggests the presence of a continuous physiological relationship between fetal size and cardiovascular response rather than a dichotomous relationship between high peripheral resistance and low cardiac output in small compared with non-small fetuses. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Influence of birth weight on fetal cardiac indices at 35-37 weeks' gestation.

OBJECTIVE: Echocardiographic studies have reported that fetuses with low birth weight, compared to those with normal birth weight, have globular hearts and reduced cardiac function. Dichotomizing continuous variables, such as birth weight, may be helpful in describing pathology in small studies but can prevent us from identifying physiological responses in relation to change in size. The aim of this study was to explore associations between fetal cardiac morphology and function and birth weight, as a continuous variable, as well as uterine artery (UtA) pulsatility index (PI), as an indirect measure of placental perfusion, and the cerebroplacental ratio (CPR), as an indirect measure of fetal oxygenation. METHODS: This was a prospective study of 1498 women with singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Pregnancies complicated by pregestational or gestational diabetes mellitus, chronic hypertension, pregnancy-induced hypertension or pre-eclampsia were excluded from the analysis. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricles. The morphology of the fetal heart was assessed by calculating the right and left sphericity indices. In addition, the PI of the UtA, umbilical artery (UA) and fetal middle cerebral artery (MCA) was determined and the CPR was calculated by dividing MCA-PI by UA-PI. Multiple linear regression models were used to assess determinants of fetal echocardiographic parameters. RESULTS: The study population included 146 (9.7%) small-for-gestational-age (SGA) fetuses with birth weight < 10th percentile and 68 (4.5%) with fetal growth restriction (FGR). In the SGA and FGR groups, compared to the non-SGA and non-FGR fetuses, respectively, there was a more globular right ventricle and reduced left and right ventricular systolic function, and, from the left ventricular diastolic functional indices, the E/A ratio was increased. There was a linear association of right ventricular sphericity index, indices of left and right ventricular systolic function and E/A ratio with birth-weight Z-score. There were no significant associations between cardiac morphological and functional indices and UtA-PI Z-score or CPR Z-score. CONCLUSIONS: This screening study at 35-37 weeks' gestation has demonstrated that birth weight is a determinant of fetal cardiac morphology and function but UtA-PI and CPR, as indirect measures of placental perfusion and fetal oxygenation, are not. This suggests that the differences in fetal cardiac indices between small and appropriately grown fetuses may be part of a normal physiological response to change in fetal size rather than part of a pathological adaptation to abnormal placental perfusion and fetal oxygenation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal cardiac function in gestational diabetes mellitus at 35-36 weeks' gestation and 6 months postpartum.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) are at increased risk for adverse cardiovascular outcome later in life. However, it is uncertain whether this increased risk is due to cardiovascular changes occurring during pregnancy and persisting thereafter or to an adverse underlying cardiovascular risk factor profile. Some studies have reported that GDM is associated with reduced systolic and diastolic left ventricular function in pregnancy; however, it remains unknown whether these changes persist after delivery. The objective of this study was to compare cardiac function and structure in women with GDM and those with uncomplicated pregnancy at 35-36 weeks' gestation and about 6 months after delivery. METHODS: This was a longitudinal study in which women with GDM and those with uncomplicated pregnancy had detailed cardiovascular assessment at 35-36 weeks' gestation and repeat examination around 6 months after delivery. In all women, left ventricular systolic and diastolic indices were measured and left ventricular mass indexed for body surface area was calculated. Cardiac output and peripheral vascular resistance were also calculated using echocardiography. Linear mixed model analysis accounting for differences in maternal characteristics was carried out to compare findings of cardiovascular function between the GDM group and controls and within each group at 35-36 weeks' gestation and at 6 months after delivery. RESULTS: We studied 73 women with GDM and 73 controls with uncomplicated pregnancy. At 35-36 weeks' gestation, women with GDM, compared to controls, had higher E/e' ratio and lower E/A ratio and global longitudinal systolic strain; there were no significant differences between the groups in ejection fraction. Left ventricular mass indexed for body surface area was also increased in women with GDM. There were no significant differences between the groups in cardiac output and peripheral vascular resistance. At 6 months after delivery, cardiac functional indices improved in both patients with GDM and controls, but in the GDM group, compared to controls, there was a lower degree of improvement in E/A ratio and global longitudinal systolic strain. CONCLUSION: In the third trimester, patients with GDM have subtle differences in diastolic and systolic left ventricular function compared to controls and, despite improvement after delivery, these changes persist for at least 6 months. Long-term follow-up is therefore needed to assess whether women with GDM are at risk for an accelerated decline in their cardiac function and, if so, whether this trend can be reversed or delayed by optimal cardiovascular risk factor modification. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Manifestation of migraine in adolescents: Does it change in puberty?

PURPOSE: To analyze the association between pubertal stage, menstrual cycle and migraine attacks in girls with migraine. In addition, headache frequency, accompanying symptoms, duration and onset in relation to the specific phase of the cycle were investigated. METHODS: Girls between 7 and 18 years old, diagnosed with headaches that met "International Classification of Headache Disorders II" diagnostic criteria for migraine without aura, kept a daily headache and menstrual cycle diary over 8 weeks. Ovulatory cycles were identified by weekly progesterone saliva tests. RESULTS: 47 girls participated in the study and were divided into three groups according to Tanner stage and onset of regular menstruation: pre- (n = 16), peri- (n = 19) and post-pubertal (n = 12). A significant difference in migraine frequency was found between pre- and post-pubertal girls (p = 0.005). No significant differences with regard to headache characteristics were detected. Interestingly, a higher frequency of attacks in follicular phase occurred compared to luteal phase in peri- and post-pubertal girls (p = 0.030). CONCLUSION: During puberty, migraine patterns in girls change to a typical adult pattern of migraine in a stepwise manner not clearly related to menarche. The first sign of this transition phase could be the higher frequency of migraine attacks in post-pubertal girls.

Etiology of rickets in Egyptian children.

Factors associated with the rickets found in children attending the Outpatients Department of Cairo Children's Hospital have been studied. All the children studied were small for their age with the rachitic children being significantly smaller than the controls. The clinical diagnosis of the disease was confirmed in 54 children by X-ray and plasma biochemistry. The best indicator of the disease was the enlarged epiphysis of the wrist and to a lesser extent that of the ankles. Some of the factors predisposing to rickets were assessed in the rachitic children and in age-matched controls. There was no difference in the nutrient intake of these two groups of children although intakes of energy, calcium and vitamin D, but not of protein, were lower than recommended dietary allowances. Although more of the rachitic children came from urban areas than the controls there were no significant differences in the environments to account for the occurrence of the disease. Factors contributing to the development of rickets are discussed with particular regard to aspects such as low body weight, low maternal vitamin D status and low calcium intakes which cause a high rate of utilization and metabolism of vitamin D.

Serotonin metabolism and depression in oral contraceptive users.

Serotonin and nicotinic acid ribonucleotide metabolic pathways of tryptophan metabolism were studied before and after tryptophan load test in thirty women using oral contraceptive steroids for a period of 2 to 5 years. Ten of them were suffering from depression. Another ten healthy women participated in this study as a control group. Twenty-four-hour urinary excretion of serotonin, 5-hydroxyindole acetic acid and total 5-hydroxyindoles were estimated as indices of serotonin pathway metabolites, while xanthrenate excretion was determined as an index of tryptophan oxygenase pathway. Plasma cortisol, urinary 17-oxosteroids and 17-hydroxycorticosteroids were determined to assess adrenal cortical function. Urinary creatinine output was assayed to check the adequacy of 24-hr urine collection. The changes induced by oral contraceptive steroids on tryptophan and corticosteroid metabolism were correlated with the associated depression. Changes in serotonin metabolism were demonstrated in the depression group before and after tryptophan load test, while in the non-depression group before and after tryptophan load test, while in the non-depression group, these changes were only demonstrated after tryptophan load test. Results indicated the alteration in tryptophan metabolism are usually well compensated in the non-depression group but may accentuate or precipitate the development of depression in susceptible women.