Histopathological Changes In Placenta Research Articles

Histopathological Changes of Placenta in Maternal Hypertensive Disorders and its Association with Birth Weight: A Case-control Study

Introduction: One of the most common complications during pregnancy is hypertension. It leads to pathological changes which reduce the placental blood flow. Hypertensive disorders are strongly associated with foetal growth restriction, prematurity, lower foetal birth weights and contribute largely to perinatal mortality and morbidity. Aim: To study the histomorphological changes of placenta in cases of maternal hypertensive disorders and compare it with normal controls as well as find out its association with neonatal birth weight. Materials and Methods: A case-control study was conducted at the Department of Pathology of a Tertiary Care Hospital, Faridabad, Haryana, India. Duration of the study was 2 months from July to August 2018. This study is a part of Indian Council of Medical Research (ICMR) Short Term Studentship (STS) scheme for MBBS students. Control group was formed by 30 placenta of full term deliveries without any complications and 30 placenta of the females presenting with hypertensive pregnancies formed the case group. Specimens of placenta were studied in detail for morphological and histological changes. Neonatal Birth weight was recorded just after delivery of all the cases and controls. Analysis of statistical difference between the means of both groups was performed using student unpaired t-test. The data obtained was entered in Microsoft excel sheet and statistically analysed using Epi Info version 7. Results: Mean maternal age for cases was 28.60 years and controls were 25.23 years. This association was found to be significant. Mean for gestational weeks at the time of delivery was 34.93 weeks in cases and 37.20 weeks in controls (p-value <0.0001). Average placental weight in cases was 410.20 grams and in controls was 480.80 grams (p-value <0.001). Histopathological changes comprised of Syncytial knot formation, Cytotrophoblasts proliferation, proliferation of endothelial lining of capillaries, stromal fibrosis, calcification, hyalinisation of villi and infarction were comparatively more frequent in cases (n=30). Mean neonatal birth weight was found to be 2809.67±128.32 grams in control group as compared 2427.67±152.22 grams in cases (p-value <0.001). Conclusion: During pregnancy significant histomorphological changes in placenta are caused due to hypertensive disorders which lead to harmful and severe foetal outcomes. A valuable insight into the mechanism of placental dysfunction can be achieved through a detailed examination after delivery.

Histopathological Changes in Placenta of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) Infection and Maternal and Perinatal Outcome in COVID-19.

BackgroundWhether vertical transmission or placental pathology occurs after maternal infection during pregnancy remains unknown. There is a clear need for studies on the impact of COVID-19 on pregnancy outcome. A systemic inflammatory or hypercoagulable state may be the contributing factor for placental pathology.MethodsThe pregnant women with COVID-19 who delivered between May 2020 and May 2021 were followed and data were collected about pregnancy course and placentas were examined for macro- and microscopical changes and were compared to controls with non-infected women. ResultsPlacenta of COVID-19-infected females had increased prevalence of decidual arteriopathy and placental injury reflecting hypoxia and uteroplacental insufficiency within the intervillous space. Features of maternal vascular malperfusion such as increased syncytial knots were present in 100% cases. Fibrinoid necrosis was seen in 100% cases and increased focal perivillous fibrin depositions were presented in 37.7% cases. About one fourth infected placentas had evidence of villitis. Even after matching for comorbidities like preeclampsia, these changes were present.ConclusionThe most common pathological findings of the placenta of COVID-19 infections are signs of maternal and fetal malperfusion. Future studies should target infections in different stage of gestation, including first and second trimesters.

A Study on Histopathological Changes and Neonatal Outcomes in the Placenta of COVID-19 Positive Mothers–A Prospective Study

context: It has been estimated that are about 168 million lab confirmed COVID 19 cases worldwide as of 28th may, 2021. Due to the high prevalence of this disease, it is of utmost importance to study its effect on the vulnerable population of pregnant women. aim: Aim of the study are 1) the histopathological changes in placenta of COVID19 mothers. 2) To correlate the histopathological changes with the fetal outcome in COVID 19 positive mothers. materials & method: Twenty five placentas of Covid 19 positive mothers were received in formalin with proper clinical history including age of the mother, gestational age, mode of delivery, complications during pregnancy and during labor, baby weight and APGAR score of the baby. The specimen were allowed to fix in neutral buffered formalin for a period of 48 hrs. The placentas were then grossly and histopathologically examined. results: Out of 25 placentas, some showed features of maternal vascular malperfusion (MVM), particularly villous infarct, villous agglutination and intervillous and perivillous fibrin deposits. Some showed fetal vascular malperfusion features like avascular villi, stem vessel obliteration were also present in a few of the cases. Out of the 25 pregnancies, 21 babies were delivered live with normal birth weight. There were 4 spontaneous abortions ranging from 14 - 22 weeks. conclusion: As the placenta acts as a bridge between the mother and the developing baby, any insult to the placenta in the form of maternal or fetal vascular malperfusion may result in an adverse perinatal outcome

To evaluate histopathological changes in placenta of IUGR

The present study entitled “To evaluate Histopathological changes in Placenta of IUGR” was conducted in the Department of Obstetrics and Gynaecology. A total of 400 patients were studied. Out of them 200 were normal patients without IUGR and 200 with IUGR. These patients were evaluated with the help of semistructured proforma consisting of various socio-demographic and clinical variables.Number of LSCS deliveries in IUGR patients (59) is significantly more than control group (33).The number of syncytial knot formation (>10) in IUGR is 169 compared to 153 of control and hence is statistically insignificant. Cytotrophoblastic proliferation (>10) in IUGR (126) is significantly more than (92) in the control group. Number Of area fibrinoid necrosis in villi > 5 in IUGR group is 57 compared to control group (29) (significantly higher) No. of hylinized areas (> 5) in IUGR (101) is significantly higher than in control group (68). Histopathological findings in low power field like syncytial knot formation, cytotrophoblastic cellular proliferation, calcification and hyalinisation of villi are also found as normal aging changes in placenta but it occur early and more frequently per low power field in IUGR group. To conclude, these morphological & histological findings of placenta are the etiological basis for Intra uterine growth restriction.

Histopathological changes in placenta in pregnancy-induced hypertensive patients and correlation with fetal outcome – a tertiary care hospital study

Histopathological changes in placenta in pregnancy-induced hypertensive patients and correlation with fetal outcome – a tertiary care hospital study

Study on Histomorphological Findings in Placenta in Cases of Pregnancy Induced Hypertension

Introduction: PIH is a common condition associated with changes in placenta. It leads to increased perinatal mortality. The present study was conducted to assess the morphological and histopathological changes in placenta in cases of pregnancy induced hypertension. Subjects and Methods: The present comparative study included 49 cases of PIH and 49 normotensive mothers. Clinical details and placental morphology were noted. Results: That the two groups are similar with no significant difference. Placental weight and diameter were similar in PIH and control groups (p>0.05). However, placental thickness and number of cotyledons were greater in PIH group (p=0.00) while placental volume was lower with significant difference (p=0.01). PIH group showed greater proportion of infarction, calcification, hyalinised area per 10 lpf and intervillous haemorrhage (p=0.00). Conclusion: PIH leads to gross and microscopic changes in placental morphology.

A study on histopathological changes in placenta in pre-eclampsia/eclampsia: A case-control study in tertiary care centre, western India

Introduction: In pregnancy induced hypertension (PIH), pathological changes in the placenta occurs which may result in reduced blood flow across placenta. The present study has been undertaken to assess the morphology & histology of placenta from mothers with PIH and to correlate their findings with those of normal pregnancies. Materials and Methods: The present study was a case-control study conducted during July 2015 to September 2017. Placenta of cases of singleton normal pregnancies & those complicated by pre-eclampsia/ eclampsia and of known gestational period were included. The placentae were divided into two groups; Group 1: Pregnancy with hypertension (cases) and Group 2: Normal pregnancy (control). Detailed macroscopic and microscopic examinations were conducted on the placentae. Results: The mean weight of placenta (474 ± 58 grams) was higher among control group in comparison to PIH group (420 ± 61 grams). This difference was statistically significant. (p 0.001) The mean fetoplacental weight ratio (6.14 ± 0.503) was higher among PIH group in comparison to control group (6.03 ± 0.409). This difference was statistically insignificant. (p ?0.05). There was significant association between presence of gross infarction, calcification, Hyalinised area /10 lpf, medial coat proliferation/ 10 lpf, intervillous hemorrhage, decreased villous vascularity and PIH. Conclusion: It is concluded that there was statistically significant difference between mean birth weight of the babies and mean placental weight in control group and PIH group. It also revealed striking villous lesions like increased syncytial knots, cytotrophoblastic cell proliferation, villous stromal fibrosis and fibrinoid necrosis in placenta from preeclampsia cases. Keywords: Placenta, Histopathological Changes, Pre-eclampsia, Eclampsia.

A novel peptide relieves endothelial cell dysfunction inpreeclampsia by regulating the PI3K/mTOR/HIF1α pathway.

Preeclampsia (PE) is a pregnancy-specific complication characterized by hypertension and proteinuria, and it is one of the primary global causes of maternal and perinatal mortality. Poor remodeling of placental arteries and endothelial dysfunction serve important roles in the pathogenesis of PE. Peptide derived from complement C4 A chain (PDCC4) was identified in our previous peptidome analysis of serum from patients with PE. The present study aimed to investigate the effect of PDCC4 on endothelial dysfunction in PE. TNF-α stimulated HUVECs were employed to mimic endothelial dysfunction in PE, and Cell Counting Kit 8 assay, wound healing assay, tube formation assay, RNA-sequencing (seq) and western blot analysis were performed using HUVECs. Moreover, an in vivo model of PE was established using pregnant rats treated with lipopolysaccharide (LPS), and blood pressure monitoring, histopathological examination, ELISA and immunohistochemistry were performed on rats. It was found that TNF-α impaired proliferation, migration and tube formation of HUVECs, but pretreatment with PDCC4 moderated these effects. RNA-seq and western blotting demonstrated that the PI3K/mTOR/HIF1α signaling pathway was activated by PDCC4, and a selective PI3K inhibitor reversed the protective function of PDCC4 on TNF-α stimulated HUVECs. Additionally, PDCC4 alleviated hypertension, histopathological changes of placenta and kidney and the expression levels of endothelial injury markers and inflammatory cytokines induced by LPS in rats. These results suggested that PDCC4 relieved endothelial dysfunction in PE via PI3K/mTOR/HIF1α signaling pathway and may be a potential therapy for PE.

Histopathological Changes of Placenta Associated with Maternal Anaemia in Northeast Ethiopia: A Comparative Study.

Anaemia during pregnancy affects about half of all pregnant mothers in developing countries; it is the major causes of indirect maternal mortality. Anaemia can directly cause poor growth of fetus in utero due to inadequate oxygen flow to the placental tissue or it is indirect indicator of maternal nutritional deficiency. Mal-development of placenta is the leading cause of maternal and perinatal mortality and an important factor of fetal growth retardation. The aim of this study was to compare histopathological changes of placenta associated with maternal anaemia. A comparative cross-sectional study was conducted from May-June, 2018 in Dessie Referral Hospital. A total of 66 placentas (33 anaemic and 33 non-anaemic) were collected after delivery. EPI data version 4.2.0 was used to enter the data while the data were analyzed by using SPSS version 22. Chi-square and one-way ANOVA were used to analyze the data. In pregnancies with maternal anaemia, 75.7% of anaemic placentas terminal villi vessels were increased in number, compared to 15.1% in non-anaemic (p=0.001). Placental calcification was 72.7% in anaemic groups compared to 54% in non-anaemic groups. However, it was insignificant (p=0.12). Intervillous space was wider in anaemic compared to non-anaemic groups (p<0.001). Chorionic villi capillaries were increased in number, and it was dilated in anaemic placenta, compared to non-anaemic. Intervillous space was significantly wider in anaemic placenta.

Histopathological Changes of Placenta Associated with Maternal Anaemia in Northeast Ethiopia: A Comparative Study

BACKGROUND: Anaemia during pregnancy affects about half of all pregnant mothers in developing countries; it is the major causes of indirect maternal mortality. Anaemia can directly cause poor growth of fetus in utero due to inadequate oxygen flow to the placental tissue or it is indirect indicator of maternal nutritional deficiency. Mal-development of placenta is the leading cause of maternal and perinatal mortality and an important factor of fetal growth retardation. The aim of this study was to compare histopathological changes of placenta associated with maternal anaemia.METHODS: A comparative cross-sectional study was conducted from May-June, 2018 in Dessie Referral Hospital. A total of 66 placentas (33 anaemic and 33 non-anaemic) were collected after delivery. EPI data version 4.2.0 was used to enter the data while the data were analyzed by using SPSS version 22. Chi-square and oneway ANOVA were used to analyze the data.RESULTS; In pregnancies with maternal anaemia, 75.7% of anaemic placentas terminal villi vessels were increased in number, compared to 15.1% in non-anaemic (p=0.001). Placental calcification was 72.7% in anaemic groups compared to 54% in non-anaemic groups. However, it was insignificant (p=0.12). Intervillous space was wider in anaemic compared to non-anaemic groups (p&lt;0.001).CONCLUSIONS; Chorionic villi capillaries were increased in number, and it was dilated in anaemic placenta, compared to non-anaemic. Intervillous space was significantly wider in anaemic placenta.

The morphological &amp; histopathological changes of placenta in pregnancies obtained by Intracytoplasmic sperm injection (ICSI)

Background: Growth of the fetus is directly related to the structure and function of the placenta, and the examination of the Placenta and umbilical cord provides us important information about what has happened to the fetus. Pregnancies induced by ART are more likely to develop pregnancy complications than other singleton pregnancies. The main cause of these undesirable pregnancy outcomes is uncertain, and perhaps morphological and histopathologic abnormalities of placenta in these types of pregnancies may be involved. Since the most common method of ART is the ICSI method, the aim of this study was to evaluate the histological changes of the placenta and umbilical cord in ICSI pregnancies. Methods: In this study, 30 women who were pregnant with ICSI method and had no pregnancy complications were compared with 30 pregnant women with normal and non-complicated pregnancies. Morphology and histology of the placenta and umbilical cord were compared in two groups. For studying with optical microscopy, samples of the placenta were prepared from two groups were stained with H & E, PAS and trichrome, and compared with the optical microscope. Results: There was no difference between the two groups in demographic variables. umbilical cord length, 1th and 5th minute Apgar score in two groups. The umbilical cord thickness (p = 0.01), and placental thickness (p = 0.02) was significantly higher in the study group. In the pathological study of placenta, it was revealed that in study group there are increased syncytial knot in staining with hematoxin and eosin, reducing of glycogen in PAS staining, and increasing the amount of fibrosis in trichrome staining compared with the control group. Conclusion: The study of pathological changes in ICSI pregnancies compared with normal pregnancies showed that the prevalence of syncytial knots (Due to the accumulation of the nucleus of apoptotic cells in the placenta) is significantly higher.

Molecular mechanisms of Cisplatin- induced placental toxicity and teratogenicity in rats and the ameliorating role of N-acetyl-cysteine

The aim of the present study is to investigate the molecular mechanisms of Cisplatin- induced placental toxicity and teratogenicity in rats and the ameliorating role of N-acetyl-cysteine (NAC). Cisplatin was administrated intraperitoneally at 5 mg/kg.b.wt as a single dose on the 12th day of gestation while NAC was administered orally throughout gestation either alone or in concomitant injection of Cisplatin at 200 mg/kg.b.wt. Cisplatin + NAC group showed reduction in the elevated morphological, visceral and skeletal abnormalities as well as the morphological and histopathological changes in placenta compared to Cisplatin - treated rats. Importantly, NAC attenuated Cisplatin-induced placental apoptosis through down-regulation of Fas and Caspase-3 genes expression. In conclusion, induction of placental apoptosis by overexpression of Fas and Caspase-3 genes gives a new insight into the mechanism of Cisplatin teratogenicity. The protective role of NAC, on the other hand, was characterized by attenuation of Fas and Caspase-3 genes- mediated apoptosis.

Histopathological Changes of Placenta in Meconium Stained Liquor and Its Relevance in Fetal Distress: A Case Control Study.

Meconium passage during labour is a quite common finding. Studies describing correlation between meconium stained liquor, fetal distress and specific placental pathology are sparse. This case control study had been designed to ascertain these lacunae of knowledge. Placentae from 41 cases of otherwise uncomplicated antenatal and intranatal pregnancies with meconium stained liquor at 37 completed weeks of gestation were studied, both grossly and microscopically, comparing them with controls of 41 cases of clear liquor. Apgar score of all newborns at 1 minute and 5 minutes were recorded and correlated with histopathological findings. Both cases and controls were found to be age matched. Meconium stained liquor was associated with more caesarian section than the clear ones. Significant correlation was found with meconium stained liquor and low Apgar scores. Histopathology of placenta revealed many statistically significant associations between specific placental histopathology in meconium stained liquor and depressed Apgar score. Evidence of placental vasculopathy rather than meconium induced placental damage came out as the potential culprit in causing a low Apgar score in this case control study. Placental vascular changes have a role in meconium staining of liquor. If timely interventions are taken, the chance of development of fetal distress is low.

Perinatal Outcome and Histopathological Evaluation of Placentas in Intrauterine Growth Restriction (IUGR) Pregnancies

Introduction: Intrauterine growth restriction (IUGR) is a condition in which fetus fails to achieve its inherent growth potential. It is the second most common cause of perinatal mortality and morbidity following prematurity. Objectives: Objectives of this study were to see the perinatal outcome and histopathological changes in placenta in IUGR pregnancies. Material & Methods: 100 cases of IUGR were taken up for study along with 50 controls. Ultrasonography was done to evaluate the uteroplacental insufficiency. Placental weight and morphology and histopathology of placenta was done. Results: Prevalence of IUGR was more in younger age group 49%, primigravida 58%, low socio economic status 96% and rural background 77%. History of IUGR in previous pregnancy was 30%. Abnormal color Doppler was found in 47%. Placental weight was less in IUGR and histopathology of placenta showed fibrinoid necrosis in 48% and syncytial knots 44%. Neonatal mortality in the study came out to be 12%. Conclusion: Regular antenatal care is necessary to pick up IUGR pregnancies and once diagnosed ultrasonography for fetal growth and color Doppler help to decide the optimal time for delivery.

Effects of prenatal maternal seizure on hippocampal damage and cognitive deficits in offspring rats

Objective: To observe hippocampal damage and cognitive impairment of offspring exposed to prenatal maternal seizure induced by amygdala kindling, and to explore the underlying mechanism by the detection of pathological changes of placenta. Method: Adult female SD rats were randomly divided into three groups: control group(8 rats), kindling group(12 rats) and sham group(8 rats). All the rats were allowed to mate after one week's fully kindling. The pregnant rats in kindling group received electric stimulation every 48 h. Dams were allowed to deliver naturally. Effects of maternal seizure on the number of offspring, the survival rate and body weight of pups were observed. HE staining was used to visualize histopathological changes of placenta. Morris water maze test was used to assess the cognitive function and Nissal's staining to detect hippocampal morphology of the offspring. One-way ANOVA analysis and χ2 test were used. Result: Compared with the sham group (95%(78/82)) and the control group (95%(82/86)), the survival rate of pups in kindling group(81%(66/82))was much lower (χ2=13.817, P=0.001). There were no significant differences in the number of pups per litter and pups birth-weight between kindling group and sham group or control group(F=0.312 and 0.257, P=0.736 and 0.776). HE staining showed that placental tissues from control and sham groups were normal whereas the histologic abnormalities of placentas from kindling group were characterized by thickening of the villus vascular walls, luminal stenosis, trophoblasts hyperplasia, abnormalities of trophoblasts with nuclear pyknosis and karyorrhexis and accumulation of inflammatory lymphocytes in labyrinthine zone. Nissl staining showed that neurons in hippocampus of P0(0 d after birth) and P84(84 d after birth) offspring from control and sham groups were normal, but neuronal damages were obvious in hippocampus of P0 and P84 offspring from kindling groups, and the damages in P0 pups were severe with a marked loss of neuron, shrinkage of cells and nuclear pyknosis and karyorrhexis. In the Morris water maze, compared with the sham group ((29±8), (19±9), (10±4)s) and the control group ((25±6), (17±5), (14±4)s) rats in the kindling group ((36±8), (29±8), (30±11)s) exhibited significantly longer escape latency from the 3rd, 4th, and 5th days (F=6.276, 7.518, 18.422, P=0.030, 0.003, 0.000), significant less time in the target quadrant ((27±8) vs.(58±11)and(68±13)s, F=35.993, P=0.000) and reduced number of crossing the platform ((4.4±1.7) vs. (7.2±1.6) and (8.5±1.3)times, F=18.377, P=0.000). In addition, there was no significant difference between control and sham groups(P all >0.05). Conclusion: The prenatal maternal seizures induced significant pathological damages to hippocampus and cognitive impairment of offspring. Hypoxia-ischemia of placenta might play an important role in this process.

Histopathological changes in placenta of a preeclampsia-like L-NAME rat model treated with sildenafil citrate

Histopathological changes in placenta of a preeclampsia-like L-NAME rat model treated with sildenafil citrate

Histopathological changes in placenta of a preeclampsia-like L-NAME rat model treated with sildenafil citrate

Histopathological changes in placenta of a preeclampsia-like L-NAME rat model treated with sildenafil citrate

Histopathological Changes in Placenta of Rat Induced by Levtricetam

Background and objectives: Levetiracetam (LEV) is an established second-generation antiepileptic drug. Its use in women with epilepsy of child-bearing potential is a delicate balance between seizure control and adverse effects to the fetus. This study has been designed to evaluate the histopathological effect of levetiracetam in different doses (Therapeutic dose & ¼ LD50), on the placenta of experimental rats. Design and Setting: This study is a randomized single blind control trail conducted from January 2009-December2009.Materials and Methods: Placentas were collected for microscopic examination on day 20 of gestation after rat’s scarification. Results: The placenta showed neither significant reduction in weight nor any overt anomaly compared to control group. Histological examination of the treated groups showed structural changes mainly in the dose of 1/4 LD50. Decidual necrosis, decrease trophospongium area, fibrinoid deposit, necrosis of labyrinth, vascular congestion and hemorrhage were observed. The results suggested that levetiracetam induced dose dependent changes in the structure of placenta. Conclusions: Therefore, levetiracetam in therapeutic dose can be used safely during pregnancy. However, its safety showed be established in a large scale randomized study with long term follow-up.

Study of structural changes in placenta in pregnancy-induced hypertension.

Background:Hypertension is one of the most common complication during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. This study was designed to investigate the morphological and histopathological changes in placenta from pregnancies complicated with hypertension.Objectives:To study the morbid changes in placenta in cases of pregnancy-induced hypertension (PIH) and to correlate the findings with birth weight of new born babies in comparison with normotensive mothers.Materials and Methods:The study was done on 100 placentas, out of which 50 were collected from normotensive mothers and the remaining 50 from PIH cases. All the placentas were studied morphologically and histologically. The birth weight of neonates was recorded.Results:In the present study it was observed that weight and dimensions of placenta was less in study group when compared with control group. The mean neonatal birth weight was more in normal pregnancy and feto-placental weight ratio was significantly high in hypertensive group. Histopathological study showed significant number of syncitial knots, areas of fibrinoid necrosis, hyalinization, calcification, and medial coat proliferation of medium sized blood vessels in hypertensive group.Conclusion:PIH significantly affects the placenta by reducing its weight and dimensions. These changes may cause placental insufficiency as a result of compromised utero-placental blood flow. Therefore has an adverse affect on the neonatal birth weight. PIH has definite influence on morphology, histology of placenta, and thus affects the growth of the fetus.

English

BACKGROUND: Maternal disorders will influence the placenta, as it forms a functional unit between the mother and the fetus. Severe anaemia has many effects on important organs. In pregnancy it is associated with late abortions, prematurity, low birth weight and stillbirths 1, 2, 3, 4, 5. Microscopic abnormalities of placenta may provide crucial information. Hence, the present study was under taken to analyse, the spectrum of histopathological changes in placenta, in severe anaemia during pregnancy. METHODS: One hundred and twelve placentas were studied of which, 56 belonged to mothers with severe anaemia and 56 belonged to mothers with normal haemoglobin. Histological sections made from placental tissue bits, taken from the central placenta were studied. Four hundred villi were counted, and different histopathological features were quantified. The mean number of villi showing syncytial knots, vasculo- syncytial membrane, fibrinoid necrosis and villous stromal fibrosis was determined. The comparison of the means was done using students unpaired't' test. Test of proportion was applied wherever necessary. RESULTS: Significant microscopic changes were observed in placentae of anaemia group as compared to controls. Villi in placentas from mothers with severe anaemia showed excessive syncytial knots (p 0.05). CONCLUSION: Severe anaemia in pregnancy alters the placental morphology and adequate treatment of anaemia may therefore be critical to normal placental function.