Clinical signs suggestive of sepsis include one or more of the following: pyrexia, hypothermia, tachycardia, tachypnoea, hypoxia, hypotension, oliguria, impaired consciousness and failure to respond to treatment. These signs, including pyrexia, may not always be present and are not necessarily related to the severity of sepsis.

RCOG Green Top guideline No: 64a. Bacteria sepsis in pregnancy-Apr 2012. http://​www.​rcog.​org.​uk/​files/​rcog-corp/​25.​4.​12GTG64a.​pdf

Women who are transfused regularly or intermittently are at risk of transfusion-transmitted infections. It is therefore important to ascertain infectivity and manage the common transfusion-related viral infections appropriately.

The majority of women with thalassaemia major will have been immunised against hepatitis B, but some women with thalassaemia intermedia may not.

Hepatitis C is a common and often asymptomatic virus, so all women who are transfused require hepatitis C antibody testing. If a woman has a positive hepatitis C test, RNA titres should be determined with referral to a hepatologist.

Women who have undergone splenectomy are at risk of infection from encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b. UK guidance is that daily penicillin prophylaxis is given to all high-risk splenectomised patients.

Beta thalassemia in pregnancy – RCOG Green Top guideline No: 66. Mar 2014. http://​www.​rcog.​org.​uk/​files/​rcog-corp/​GTG_​66_​Thalassaemia.​pdf

Acute fatty liver of pregnancy (AFLP) in most cases needs to be differentiated from HELLP syndrome. Both conditions are common in primiparous women. HELLP is characterised by hypertension, proteinuria and epigastric pain with or without vomiting.

Vomiting is seen more commonly in AFLP. Coagulopathy is seen more commonly in AFLP and may cause severe and life-threatening postpartum haemorrhage. The other changes that may help differentiate these two conditions are haematological—thrombocytopenia occurs in HELLP, whereas raised WBC counts are more common in AFLP. AFLP carries a high maternal and fetal mortality of between 2–18 % and 7–58 % respectively. Other complications include renal failure, pancreatitis and (transient) diabetes insipidus. There is also a risk of progression to hepatic encephalopathy and fulminant liver failure.

Cuckson C, Germain S. Hyperemesis, gastrointestinal and liver disorders in pregnancy. Obstet Gynaecol Reprod Med. 2013;21:3.

Wernicke’s encephalopathy is a complication of hyperemesis gravidarum which occurs due to lack of thiamine (vitamin B1). It can occur following any condition leading to imbalanced nutrition lasting for 2–3 weeks. It carries a mortality of 10–15 % and if uncorrected may lead to Korsakoff’s encephalopathy where the patient develops antegrade and retrograde amnesia and confabulation. The management of hyperemesis includes thiamine replacement 50 mg po tds or 100 mg IV daily for 3 days. Another option especially in moderate to severe vomiting is to administer Pabrinex which is multivitamin intravenous supplement containing 250 mg of thiamine along with riboflavin, pyridoxine, nicotinamide and vitamin C.

Cuckson C, Germain S. Hyperemesis, gastrointestinal and liver disorders in pregnancy. Obstet Gynaecol Reprod Med. 2013;21:3.

Obstetric cholestasis is a pregnancy-specific condition characterised by maternal pruritus and altered liver function tests. The common abnormality seen is elevated serum bile acids, but derangement in other markers of liver function such as transaminases, bilirubin and GGT (gamma-glutamyl transferase) also occurs. Other maternal symptoms include steatorrhoea, pale stools and dark urine. The risk of stillbirth is difficult to predict despite CTG monitoring and ultrasound for fetal well-being. Studies show that the risk to fetus may be related to the level of bile acids in the scrum with a 1–2 % increase in risk of death for every 1 mmol/L increase in bile acids.

Cuckson C, Germain S. Hyperemesis, gastrointestinal and liver disorders in pregnancy. Obstet Gynaecol Reprod Med. 2013;21:3.

The FDA has established five categories to indicate the potential of a drug to cause birth defects if used during pregnancy. The categories are determined by the reliability of documentation and the risk to benefit ratio. They do not take into account any risks from pharmaceutical agents or their metabolites in breast milk. The categories are:

Cyclophosphamide is a category D drug which is fetotoxic and teratogenic and needs to be stopped 3 months prior to conception.

McCarthy F, Germain S. Connective tissue disorders and dermatological disorders in pregnancy. 2013;23(3):71–80.

The half-life of thyroxine-binding globulin [TBG; the main binding protein for thyroxine (T4) and triiodothyronine (T3)] is prolonged by oestrogen-driven sialylation, which results in an increased circulating concentration of both TBG and of total T4 and T3. It is for this reason that these hormones are not measured in pregnancy. Instead, freeT4 and freeT3, the biologically active hormones, are measured: these are not greatly changed in normal pregnancy, although the lower limit of normal is reduced slightly in the third trimester. Normal values for thyroid-stimulating hormone (TSH) rise slightly in the third trimester, but otherwise are unchanged compared with non-pregnant ranges.

TSH and T3 do not cross the placenta. In the first trimester, T4 does cross the placenta and is believed to play a role in fetal brain development prior to the onset of fetal thyroid activity, which occurs late in the first trimester.

Girling J, Cotzias C. Thyroid and other endocrine disorders in pregnancy. Obstet Gynaecol Reprod Med. 17(12):349–55.

Pregnancy does not affect the long-term course of hyperthyroidism. In the first trimester, there may be deterioration in control, due to reduced absorption of medication secondary to vomiting or to hCG-driven stimulation of TSH receptors. In the second and third trimesters, typically, treatment doses can be reduced as the immune effects of pregnancy result in an increase in TSH receptor inhibitory antibodies and a fall in the stimulatory ones: one third of women will be able temporarily to discontinue treatment at this time. The majority need to return to their prepregnant doses in the puerperium to prevent a disease flare. The drugs usually used propylthiouracil (PTU) and carbimazole, are safe in pregnancy and should not be stopped because of concerns about teratogenicity.

Older studies have linked carbimazole with aplasia cutis—a very rare condition resulting in deficits in the scalp and hair growth, but larger more recent studies show that either this link is spurious or at worst that the risk of the fetus developing this condition is extremely small. Both agents cross the placenta in similar amounts and, rarely, can cause fetal hypothyroidism: this risk can be minimised by ensuring that the patient takes the lowest doses of treatment to keep her clinically euthyroid and biochemically at the upper limit of the normal range. Fetal hypothyroidism rarely manifests clinically, in part because of the opposing stimulatory effect of transplacental TSH receptor antibodies.

Girling J, Cotzias C. Thyroid and other endocrine disorders in pregnancy. Obstet Gynaecol Reprod Med. 17(12):349–55.

Presentation of hypopituitarism is with lethargy, hypothyroidism, failure to lactate, amenorrhoea and adrenocortical insufficiency. Women need hormone replacement therapy (hydrocortisone, thyroxine and oestrogen) to maintain normal metabolism and response to stress. Women will need ovulation induction to conceive in the future, and glucocorticoid and thyroxine replacement must continue throughout pregnancy, with extra hydrocortisone to cover the stress of labour or intercurrent illnesses. Mineralocorticoid replacement is often not needed as aldosterone production is not solely ACTH dependent. Untreated, those women who manage to conceive have a very poor pregnancy prognosis, with high rates of miscarriage, stillbirths and maternal death, all of which can be normalised with adequate therapy.

Girling J, Cotzias C. Thyroid and other endocrine disorders in pregnancy. Obstet Gynaecol Reprod Med. 17(12):349–55.

Hypothyroidism is a common cause of hyperprolactinemia. The hyperprolactinemia of hypothyroidism is related to several mechanisms. In response to the hypothyroid state, a compensatory increase in the discharge of central hypothalamic thyrotropin-releasing hormone results in increased stimulation of prolactin secretion.

Furthermore, prolactin elimination from the systemic circulation is reduced, which contributes to increased prolactin concentrations. Primary hypothyroidism can be associated with diffuse pituitary enlargement, which will reverse with appropriate thyroid hormone replacement therapy

The causes of hyperprolactinemia are represented in this image

1. Serri O, et al. CMAJ. 2003;169:575–81.

2. Girling J, Cotzias C. Thyroid and other endocrine disorders in pregnancy. Obstet Gynaecol Reprod Med. 17(12):349–55.

Carbohydrate metabolism, especially in the third trimester, is directed towards providing the growing fetus with glucose and amino acids and liberating more free fatty acids, ketone bodies and glycerol as substrates for maternal energy. In normal pregnancy, hyperplasia of the islet cells of the pancreas results in increased levels of circulating insulin with an early increase in insulin sensitivity followed by resistance as pregnancy progresses. Thus, fasting glucose levels are 10–20 % lower due to increased glucose uptake from the maternal circulation by the growing fetus, reduced hepatic gluconeogenesis, increased peripheral glucose uptake and increased glycogenesis. Maternal insulin resistance results from placental production of diabetogenic hormones: growth hormone, placental lactogen, corticotrophin-releasing hormone and progesterone. In women with established diabetes, insulin requirements increase substantially as pregnancy progresses and until the third stage of labour when resistance falls rapidly following expulsion of the placenta.

Chaudry R, Gilby P, Carroll PV. Pre-existing (type 1 and type 2) diabetes in pregnancy. Obstet Gynaecol Reprod Med. 17(12):339–44.

Women with diabetes should be delivered in consultant-led maternity units with access to senior medical, obstetric and neonatal staff. The progress of labour should be monitored closely as for any other high-risk woman with continuous electrical fetal monitoring and regular glycaemic checks. Good glycaemic control should be maintained during labour and delivery to reduce the risk of neonatal hypoglycaemia. The target range for blood glucose concentration during labour and delivery recommended by Diabetes UK is 4–6 mmol/L. Intravenous insulin is commenced in women taking subcutaneous insulin when labour is anticipated and NPH insulin is discontinued. Normoglycaemia can be achieved using concomitant saline; however, at the start of active labour, insulin requirements fall rapidly, and therefore glucose must be given with insulin to prevent maternal hypoglycaemia (infusion rate of around 2.55 mg dextrose/kg/min). Capillary blood glucose must be checked at least hourly and the rate of insulin-adjusted accordingly.

Chaudry R, Gilby P, Carroll PV. Pre-existing (type 1 and type 2) diabetes in pregnancy. Obstet Gynaecol Reprod Med. 17(12):339–44.

NICE guideline. Diabetes in pregnancy. CG 63.

Metformin is used in some cases in early pregnancy possibly due to increased use in women with polycystic ovarian syndrome. The FDA has classified the drug as a pregnancy category B medication, meaning that it does not appear to cause harm to the fetus in animal studies. No adverse outcomes have been reported in pregnancy. It may be safe and effective, but currently no oral agents are licensed for use in pregnancy. Ideally, women with Type 2 DM on oral agents should be switched to insulin prior to pregnancy so that glycaemic control is not jeopardised. The most serious potential side effect of metformin use is lactic acidosis; this complication is very rare, and the vast majority of these cases seem to be related to comorbid conditions, such as impaired liver or kidney function, rather than to the metformin itself.

Chaudry R, Gilby P, Carroll PV. Pre-existing (type 1 and type 2) diabetes in pregnancy. Obstet Gynaecol Reprod Med. 17(12):339–44.

NICE guideline. Diabetes in pregnancy. CG 63.

HAPO (Hyperglycaemia And Pregnancy Outcomes) study in which more than 23, 000 women had a 75 g glucose tolerance test (GTT), and in those with a fasting plasma glucose below 5.8 or a 2-h value below 11.1 mmol/L, were blinded to the clinicians and women.

The four primary outcomes for which the study was powered included macrosomia (birth weight >90th centile for gestational age, gender, parity, ethnicity and field centre), primary caesarean delivery, clinical neonatal hypoglycaemia and hyperinsulinemia (cord serum C-peptide > 90th centile for the study group as a whole). A number of secondary outcomes were also considered. These included preterm birth; shoulder dystocia and/or birth injury; sum of skinfold thicknesses >90th centile for gestational age, gender, ethnicity, parity and field centre; percent body fat >90th centile for gestational age; admission for neonatal intensive care; hyperbilirubinemia; and pre-eclampsia. Results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels and the other primary outcomes. There was an association with the secondary outcomes as well but not as strong.

Hyperglycemia and adverse pregnancy outcomes. The HAPO study cooperative research group. N Engl J Med. 2008;358:1991–2002.

One of the major determinants of the risk for development of subsequent type 2 diabetes is ethnic origin. Thus, GDM may affect as many as 15 % of south Asian women in different populations, while for Caucasian women overall risk of type 2 diabetes is lower. In addition to ethnic origin, of the many potential risk factors, maternal age and body mass index appear to be among the strongest predictors of GDM. The other risk factors include previous history of GDM, previous history of still birth/congenital abnormality or a family history of diabetes. However, even a combination of risk factors does not reliably predict the likelihood of developing GDM, missing up to 50 % of cases in population-based studies.

Fraser R, Heller S. Gestational diabetes: aetiology and management. Obstet Gynaecol Reprod Med. 17(12):345–48.

Maternal obesity is associated with a significant risk of thromboembolism during both the antenatal and postnatal period. Case-control studies assessing the risk show a significant association between venous thromboembolism and BMI ≥30 with odds ratio of 2.7–5.

The RCOG Clinical Green Top Guideline No. 37 advises that:

RCOG guideline No. 37a. Reducing risk of thrombosis and embolism in pregnancy and peurperium. RCOG /CMACE joint guideline– management of women with obesity in pregnancy – March 2010.

Serum ferritin is a stable glycoprotein which accurately reflects iron stores in the absence of inflammatory change. It is the first laboratory test to become abnormal as iron stores decrease, and it is not affected by recent iron ingestion. It is generally considered the best test to assess iron deficiency in pregnancy, although it is an acute phase reactant and levels will rise when there is active infection or inflammation. During pregnancy, in women with adequate iron stores at conception, the serum ferritin concentration initially rises, followed by a progressive fall by 32 weeks to about 50 % pre-pregnancy levels. This is due to haemodilution and mobilisation of iron. The levels increase again mildly in the third trimester. Even though the ferritin level may be influenced by the plasma dilution later in pregnancy, a concentration below 15 μg/l indicates iron depletion in all stages of pregnancy. In women of reproductive age, a level <15 μg/l has shown specificity of 98 % and sensitivity of 75 % for iron deficiency, as defined by no stainable bone marrow iron.

There are a variety of levels for treatment, quoted in different studies, but in general, treatment should be considered when serum ferritin levels fall below 30 μg/l, as this indicates early iron depletion which will worsen unless treated. Van den Broek et al. found that serum ferritin is the best single indicator of storage iron provided a cut-off point of 30 μg/l is used, with sensitivity of 90 % and specificity 85 %. Concurrent measurement of the C-reactive protein (CRP) may be helpful in interpreting higher levels, where indicated. The CRP concentration seems to be independent of pregnancy and gestational age, although some studies describe a mild increase.

1. UK guidelines on the management of iron deficiency in pregnancy British committee for standards in haematology 2011. http://​www.​bcshguidelines.​com/​documents/​UK_​Guidelines_​iron_​deficiency_​in_​pregnancy.​pdf

2. Van den Broek NR, Letsky EA, White SA, Shenkin A. Iron status in pregnant women: Which measurements are valid? British J Haemat. 1998;103:817–24.