• 1.
  

  a) T b) T c) T d) F e) T

Around 1 in 250 pregnant women have diabetes. Evolving data, including a meta-analysis suggest that outcomes in type 1 diabetes are as bad, and possibly worse compared with type 2 diabetes. The explanation is not entirely clear, but may include lack of pregnancy planning, older age, concomitant drug use and increased prevalence of vascular disease. Despite evidence that pregnancy planning can reduce adverse outcomes, fewer than 50% women plan their pregnancy as indicated by HbA1c documentation in the 6 months prior to pregnancy, HbA1 at booking, taking folic acid prior to pregnancy etc. The UK Confidential Inquiry into Maternal and Child Health (CEMACH) showed that only 25–30% of women with type 2 diabetes compared with 40% of women with type 1 diabetes planned their pregnancy. Near normal glucose control before and in the peri-conceptual period have been shown to reduce both miscarriages and congenital malformations. However, the HbA1c target <6.1% is achieved by fewer than 10% of women, and hence the important message is that any reduction in HbA1c towards this target reduces the individual risk.

• 2.
  

  a) T b) T c) T d) T e) T

UK NICE recommendation is that both pre and post-prandial self-monitoring should be performed. The postprandial target is < 7.8 mmol/l 1h after meals (first bite). The evidence for this comes from observational data which showed the relevance of postprandial glycemia to fetal growth. In addition a randomized trial of post vs pre-prandial monitoring reported a significantly reduced incidence of pre-eclampsia (3% vs 21%; p < 0.05) and smaller neonatal triceps skinfold thickness with post-prandial monitoring (4.5 vs 5.1; p = 0.05). In a nationwide Danish study, microalbuminuria in early pregnancy among women with type 1 diabetes was associated with a fourfold increased risk of developing preeclampsia. The prevalence of pre-eclampsia was 40% in women with micro-albuminuria compared with 12% in women with normo-albuminuria. There is an increased risk of hypoglycaemia in women with insulin-treated diabetes during pregnancy, compounded by the need for intensification of insulin therapy, and hence treatment needs to be individualised. Severe hypoglycaemia, affecting up to 40% of women, causes substantial morbidity (seizures, fractures, road traffic accidents) and is the leading cause of death in type 1 diabetic pregnancy. The risk is highest during the first trimester when insulin sensitivity improves and pregnancy-related nausea and vomiting occur. Other mechanisms include impairment of counter-regulatory response to hypoglycaemia and diminished hypoglycaemia awareness. Use of systemic steroids for fetal lung maturity is not contraindicated in women with diabetes. There is, however, a need for close monitoring of capillary blood glucose levels during this time given the significant increase in insulin requirements up to 50%. Umbilical artery ultrasound has been shown to be a better predictor of fetal outcomes in women with diabetes compared with cardiotocography or biophysical profile.

• 3.
  

  a) T b) F c) F d) F e) T

In the HAPO study, obesity and GDM (as defined by the new IADPSG criteria) were independently predictive of fetal macrosomia, pre-eclampsia, primary Caesarean delivery and neonatal adiposity. Macrosmia was more likely when GDM was present in the absence of obesity (OR 2.19; 95% CI 1.93–2.47) than when obesity was present in the absence of GDM (OR 1.73; 95% CI 1.50–2.00) and the independent effects of GDM and obesity were additive. Two large RCTs suggested that 80-90% of women with GDM can be managed by dietary therapy alone. Accelerated fetal growth will reduce the threshold for insulin therapy in women with GDM if results are borderline, but, per se, would not be an indication for insulin therapy if the results of home blood glucose monitoring were all within target. All women with previous GDM should undergo an oral glucose tolerance test 6–12 weeks after delivery using a 75g OGTT. Current NICE recommendations which suggest fasting glucose as an alternative, were based on limited evidence and miss a substantial number of cases with post load glucose intolerance (eg IGT or overt diabetes). As many as 20% of women may have impaired glucose tolerance during the early postpartum period. Type 2 diabetes develops in 50-75% of obese (BMI>30) women with a history of GDM vs fewer than 25% of women with GDM whom attain normal weight after delivery. A systematic review and meta-analysis found that women with GDM were at significantly higher risk of subsequent type 2 diabetes than women with normo-glycaemic pregnancies (RR 7.43; 95% CI 4.79–11.51); 20 cohort studies including 675, 455 women of whom 10,859 had type 2 diabetes. The relative risk was 4.69 in first five years after delivery and 9.34 more than 5 years after delivery. A population based study reported an incidence of type 2 as 3.7% at 9 months postpartum, 4.9% at 15 months postpartum, 13.1% at 5 years postpartum and 18.9% at 9 years postpartum (vs 2% in controls without GDM).

• 4.
  

  a) F b) F c) T d) F e) F

Pregnancy losses are one of the major signs of the obstetric APS, however chromosomal abnormalities and maternal hormonal or anatomical defects should be excluded before early pregnancy loss (before week 10) can be attributed to aPL. Pre-embryonic and embryonic losses (before the 10 ^th week of gestation) are frequent events in the general population, due in most cases to genetic abnormalities. Recurrent (three or more) early pregnancy losses are more rare, and among other causes, APS plays a definite role. Fetal death (after the 10 ^th week of gestation) is infrequent in the general population, but typical for the APS. Arterial hypertension may be present in a patient with APS who subsequently becomes pregnant or it may develop as the first sign of preeclampsia or the HELLP syndrome during pregnancy. Apart from these complications, hypertension in pregnancy is not a typical sign of the obstetric APS. Pre-eclampsia has been reported to be highly prevalent in patients with APS, being the major contributor to preterm delivery in these patients. Several studies have found an association between early onset, severe preeclampsia and presence of aPL. Preeclampsia in late pregnancy or near term with mild symptoms is not typical for the obstetric APS. Although infarction, necrosis and thrombosis can be seen in placentas from women with APS, these histological abnormalities are non-specific and are not always present in the placenta of women with APS. There is no good correlation between histology of the placenta and pregnancy outcome.

• 5.
  

  a) T b) F c) F d) F e) F

Spontaneous improvement of symptoms is observed in a majority of pregnant RA patients, actually in 75% of RA women who do not have autoantibodies to rheumatoid factor (RF) or citrullinated proteins (ACPA). Autoantibodies to rheumatoid factor (RF) or citrullinated proteins (ACPA) are predictors for disease activity during pregnancy. RA women positive for RF or ACPA have only a 40% chance of improving spontaneously during pregnancy. Adverse pregnancy outcomes are much less frequent in pregnant women with RA or AS than in women with SLE or APS. This is particularly true for patients with mild or moderate disease activity before and during pregnancy. In pregnant RA or AS patients who have moderate disease symptoms and don’t require immunosuppressive therapy or high dose corticosteroids, the rate of miscarriage, stillbirth, prematurity, and small for gestational age infants is within the limits for healthy women. Development of congenital heart block is independent of the mother’s diagnosis, but associated with the presence of anti-Ro/SSA or anti-La/SSB antibodies. The latter can occur in women with different rheumatic diseases as well as in healthy women without rheumatic disease.

• 6.
  

  a) F b) F c) T d) F e) F

50% of women with AS are active during pregnancy with aggravation of pain and stiffness in the spine, enthesitis and attacks of peripheral arthritis. Adverse pregnancy outcomes are much less frequent in pregnant women with AS than in women with SLE or APS. This is particularly true for patients with mild or moderate disease activity before and during pregnancy. In pregnant AS patients who have moderate disease symptoms and don’t require immunosuppressive therapy or high dose corticosteroids, the rate of miscarriage, stillbirth, prematurity, and small for gestational age infants is within the limits for healthy women. As a rule, women with AS can give birth by vaginal delivery. Inflammation or ankylosis of the sacroiliac joints as in AS is not a mechanical hindrance for the progression of parturition and vaginal delivery. Development of congenital heart block is independent of the mother’s diagnosis, but associated with the presence of anti-Ro/SSA or anti-La/SSB antibodies. The latter can occur in women with different rheumatic diseases as well as in healthy women without rheumatic disease.

• 7.
  

  a) T b) F c) T d) T e) T

vWD is the most common congenital haemostatic disease in pregnancy while ITP is the most common acquired haemostatic disease in pregnancy (while gestational thrombocytopenia is common it can hardly be characterised as a disease). vWF levels often normalise in the third trimester but this must be confirmed in vWD patients prior to delivery or other invasive procedures. vWF levels drop to pre-pregnancy levels during the post-partum period and this can lead to delayed post-partum bleeding in vWD patients. For vWD patients requiring a boost in vWF levels, DDAVP provides a safe, transient option in those proven to respond. Otherwise exogenous vWF should be administered in the form of factor infusions (e.g. Humate-P).

• 8.
  

  a) F b) F c) T d) F e) F

Meta-analyses of large cohort studies exclude an association between mild pre-eclampsia and thrombophilia. Furthermore, meta-analyses also demonstrate no benefit to antepartum anticoagulants in women, with or without thrombophilia, with non-severe pre-eclampsia. Oral anticoagulants are teratogenic in pregnancy; low molecular weight heparin is the anticoagulant of choice in pregnancy. Currently, weak thrombophilias are an indication for postpartum prophylaxis and the combination of a thrombophilia with the additional VTE risk factor of pre-eclampsia warrant postpartum prophylaxis. The duration of this prophylaxis is controversial but should be administered at least while in hospital, with most authorities recommending they be continued throughout the postpartum period (i.e. 6 weeks) whereas none would suggest extending the prophylaxis to 6 months postpartum.

• 9.
  

  a) F b) F c) T d) F e) F

Non-imaging tests (D-Dimer and clinical decision rules) to exclude DVT or PE in pregnancy have not been adequately validated to use in pregnancy. Leg compression ultrasound imaging is a reasonable first step in women with suspected PE as it involves no radiation exposure to mother or foetus. In the presence of leg symptoms the yield is higher and should be pursued in this case. If these ultrasounds were negative we would recommend V/Q scan but a CT scan based approach is also reasonable.

• 10.
  

  a) F b) T c) F d) F e) F

Cyclophosphamide is an alkylating agent and may be associated with fetal myelosuppression, toxicity or demise. Imatinib has been associated with various abnormalities. Bortezomib has resulted in fetal loss and low birth weight in animal studies. Lenolidomide is closely related to thalidomide, a well-known teratogen. Interferon-alpha is generally considered to be safe for administration during pregnancy.

• 11.
  

  a) T b) T c) F d) T e) T

The presence of congenital single kidney defines an obvious, persistent abnormality at imaging. Even if the long-term risk of end stage kidney disease in patients with a single kidney is not fully understood, and kidney function is normal in the absence of other diseases, in the absence of studies on pregnancy outcomes in congenital single kidney, we suggest extending the notes of caution for kidney donors, considering a two-fold increase in PET incidence. The morphological abnormalities observed at kidney biopsy are, as a rule, persistent; hence, even in the presence of clinical remission, IgA nephropathy should be considered a CKD. e-GFR 65 mL/min before pregnancy does not define the presence of CKD, in the absence of any other sign of kidney disease (such as proteinuria, haematuria, tubular derangements or kidney scars). Such levels may be normal in vegan women, since GFR is physiologically lower in vegan-vegetarians, or in women of very small body-size. However, since GFR is usually higher in young individuals, a careful nephrological evaluation is indicated. Multiple kidney cysts also define a persistent abnormality at imaging; they are rare in young individuals and may be the sign of ADPKD or of other congenital cystic kidney diseases. Regardless of their size, kidney scars define the presence of CKD. These patients should be considered at higher risk of upper UTI in pregnancy. We recommend applying the same protocols suggested for the prevention of recurrent UTI in pregnancy, i.e., prescribing urinary cultures every 1-2 weeks, taking into account the fact that UTIs are frequently non symptomatic in pregnancy and that the mean interval from lower to upper UTI is usually considered as being of 1–2 weeks.

• 12.
  

  a) F b) T c) T d) T e) F

The results regarding pregnancy on dialysis are improving and presently over 75% of the pregnancies that surpass the early phases are successful. The success rate may reach 90% in patients treated by long-hour dialysis (up to 6–8 hours, 6–7 days per week), thus underlining the importance of mimicking physiological function through dialysis in order to improve the results. Pregnancy has been reported on haemodialysis, the most widely used modality all-over the world, as well as on peritoneal dialysis (PD). An increase in dialysis efficiency is a clue for success also on PD; the importance of physiological depuration is also in keeping with the better results observed in patients with residual renal function or who started chronic dialysis during pregnancy. A large, recent study strongly correlated the hours of dialysis with the results of pregnancy, thus supporting previous smaller, non-systematic reports. There are very few studies on pregnancy rates on dialysis and after transplantation; overall, a 1:10:100 ratio may summarize the reduction of the probability of a live born baby in the overall population versus transplantation versus dialysis. No increase in fetal malformations has been reported in children from on-dialysis mothers; however, these children are at risk of prematurity that, besides the most commonly known neurological or metabolic effects, may lead to a higher risk of hypertension, proteinuria and CKD later in life.

• 13.
  

  a) F b) F c) F d) T e) F

Differential diagnosis between CKD and PET is greatly helped by the availability of pre-pregnancy data; however, there are at least two situations in which the diagnosis may be impossible solely on clinical grounds: the onset of a kidney disease in pregnancy, or the flare-up of an immunological disease previously in remission. This may be, among others, the case of SLE or of several forms of glomerulonephritis. The presence of early and severely impaired utero-placental flows is a hallmark of PET. Conversely, the presence of proteinuria and hypertension with normal flows suggests the presence of CKD. Even if the correlation was found to be highly significant, the relationship is not close enough to allow clinical distinction based on this parameter alone. Furthermore, the possibility of CKD superimposed on PET should be kept in mind. Even if haematuria is common in CKD, this finding is non-specific, as it may be a sign of urological disorders and may even be of vaginal origin, in particular in pregnancy. Hence, this finding, that has to be accurately evaluated, is not however synonymous with CKD. A normal s-Flt1/PlGF ratio suggests CKD, at least according to a previous study; this finding is in keeping with the hypothesis that placentation is normal, at least in the first phases of pregnancy in CKD patients, unlike PET. The degree of proteinuria is neither a hallmark of CKD nor is it strictly correlated with the severity of PET. Indeed, at least in some diseases, such as diabetic nephropathy or SLE, proteinuria may have a sudden onset and increase rapidly, similarly to PET.

• 14.
  

  a) F b) F c) T d) F e) F

Severe chest and back pain that requires opiates in order to relieve the pain is not a normal symptom in pregnancy and requires urgent investigation. In the absence of ECG evidence of ST elevation MI then aortic dissection should be excluded with an urgent CT scan. The risk of this is higher in the later stages of pregnancy and early post-partum period. Although there is a small risk associated with radiation exposure, this is outweighed by the benefit of confirming the diagnosis. Facilities to perform urgent CT scan are more widely available than MRI and heavily pregnant women may not be able to be accommodated within the confines of an MRI scanner.

• 15.
  

  a) F b) T c) T d) F e) T

Therapeutic dose warfarin provides better maternal anticoagulation but is associated with risk of fetal bleeding. The metabolism and bioavailabiliy of Warfarin may change during pregnancy and therefore the dose required to maintain the INR in the therapeutic range may be different than in the non-pregnant state. Sub-therapeutic warfarin therapy leaves the mother exposed to the risk of valve thrombosis while still exposing the fetus to bleeding risk. Continuous unfractionated intravenous heparin provides less predictable anticoagulation than LMWH and has been associated with higher rates of thrombotic complications.

• 16.
  

  a) F b) F c) T d) T e) F

ACEI are associated with fetal toxicity and are therefore not recommended during pregnancy. Beta-blockers with the exception of Atenolol are considered acceptable but may cause intra-uterine growth restriction and so fetal growth monitoring is required.

• 17.
  

  a) F b) F c) T d) T e) T

Bile acids are raised in cholestasis and not acute fatty liver, however the multiple end organ dysfunction seen in AFL commonly leads to raised creatinine. Pruritis is caused by raised bile acids and not a feature of AFL. Like most conditions AFL is more common in multiple pregnancy.

• 18.
  

  a) T b) F c) F d) T e) T

Hepatitis C, like Hep B is blood borne. Hepatitis B is not an indication for delivery by CS as many women are low infectivity and the baby can be vaccinated after birth. Hep C is indeed not a contra-indication to breast feeding as it is not transmitted this way. Hep B vaccination in at risk women is safe after the first trimester as it is not a live virus vaccine.

• 19.
  

  Azathioprine in pregnancy appears to be safe and maternal wellbeing is vital for women with autoimmune hepatitis. Treatment with interferon and ribavirin in hepatitis C infection is recommended to commence only when active disease is found. Penicillamine, as with azathioprine, is still needed for Wilson’s disease. Endoscopy and ligation banding of oesophageal varices is essential as rupture is life threatening. In women with liver transplants, pregnancy outcomes are indeed improved if conception is delayed by at least one year following surgery.

• 20.
  

  a) F b) T c) T d) T e) F

Severe hypertension, defined as a systolic blood pressure (sBP) ≥160mmHg and/or a diastolic BP (dBP) ≥110mmHg confirmed after 15 minutes, is a risk marker for stroke. The BP measurement must be repeated in 15 minutes to confirm, and if it is elevated, the woman needs medical management. It is not appropriate to send her home to return on the following day for repeat assessment. This would be appropriate only for non-severe hypertension (i.e., BP 140–159/90–109mmHg) when pre-eclampsia is not suspected and BP is not substantially different from what it has been on previous visits. This woman should receive antihypertensive therapy. In their 2011 pre-eclampsia/eclampsia guidelines, the World Health Organization (WHO) recommended as ‘strong’ the recommendation to treat severe hypertension with antihypertensive therapy. All international pregnancy hypertension guidelines agree on this point. The route of administration may be parenteral or oral, depending on the urgency of the situation; most women with severe hypertension in pregnancy do not have clear end-organ dysfunction and it is appropriate to lower their BP over hours. Increasingly, there is international agreement that pre-eclampsia should be defined broadly, as gestational hypertension with one/more suggestive maternal symptom (e.g., headache/visual disturbances), signs (e.g., oxygen saturation <97%) or abnormal laboratory test (e.g., elevated liver enzymes). Proteinuria is not a mandatory requirement. Magnesium sulphate (given for eclampsia prevention, eclampsia treatment, or fetal neuroprotection) may lower BP transiently 30 minutes after a loading dose, but MgSO ₄ should not be regarded as an antihypertensive. There is no sustained lowering of BP seen and if this is desirable clinically, as it is in the patient presented, an antihypertensive agent should be used.

• 21.
  

  a) F b) F c) F d) T e) F

Women treated with MgSO4 have low rates of respiratory depression. Even in under-resourced settings, reported rates are <10% (mean 1.3%). Although there is interest in MgSO ₄ regimens involving loading dose only, lower loading or maintenance doses, or abbreviated courses postpartum, the benefits and risks of these modified MgSO ₄ protocols are uncertain. Even if there is complete renal shut-down, a loading dose of MgSO ₄ (either 4g iv or 10gIM) will not result in potentially toxic serum Mg levels. It is during ongoing therapy that monitoring for toxicity is required, and this should be clinical unless the woman is at increased risk of toxicity (e.g. renal dysfunction). Women receiving MgSO ₄ for eclampsia treatment or prevention rarely require calcium gluconate. Even in under-resourced settings, calcium gluconate was administered in only 0.2% of MgSO ₄ -treated pregnant women. In the landmark Eclampsia Trial (of MgSO ₄ for eclampsia treatment) and Magpie Trial (of MgSO ₄ for eclampsia prevention in women with pre-eclampsia), benzodiazepines were not used to terminate eclampsia in the MgSO ₄ arms. Eclampsia is usually transient, and even if it is not, diazepam (vs. MgSO ₄ ) for eclampsia was associated with higher maternal mortality in the Eclampsia Trial.

• 22.
  

  a) T b) F c) T d) F e) T

Antihypertensive therapy for non-severe hypertension in pregnancy will lower the risk of severe hypertension without increasing problems for the baby. It is recommended based on the results of the CHIPS Trial. Captopril is contraindicated for use before delivery, because of a risk of fetal nephro-toxicity. However, captopril is acceptable for use after delivery and during breastfeeding. The most common antenatal antihypertensive agents used are methyldopa, labetalol, and nifedipine XL. The target blood pressure for this woman should be <140/90mmHg. This is also the target BP for women with non-severe hypertension outside pregnancy, even in the presence of co-morbidities. The only exception is women with type 1 pre-gestational diabetes mellitus who should be treated outside pregnancy to a target of <130/80mmHg; there are no data to guide whether this is an acceptable goal in pregnancy. Antihypertensive therapy does not lower the risk of pre-eclampsia among women with pre-existing hypertension or the risk of progression to pre-eclampsia among women with gestational hypertension.

• 23.
  

  a) F b) F c) T d) T e) T

The highest postpartum blood pressure is on days three to six after delivery. At that point, hypertension may appear for the first time or antenatal hypertension may worsen. Most antihypertensive agents used postpartum are acceptable for use in breastfeeding. Care providers can access the National Institutes of Health (NIH) LactMed database on drugs in breastfeeding, for up-to-date guidance on this topic ( ). Clonidine is not recommended in breastfeeding because of high serum levels of the drug in breastfed infants. Pre-eclampsia may develop for the first time postpartum. Any woman who develops hypertension or symptoms consistent with pre-eclampsia (e.g., headache) should be evaluated for pre-eclampsia with the appropriate clinical and laboratory assessment. Pre-eclampsia may also worsen postpartum in women with antenatal pre-eclampsia. Women who have experienced a hypertensive disorder of pregnancy are at increased risk of future hypertension and cardiovascular disease. They should have regular checks of their BP. Whether or not they should be screened earlier or more intensively for cardiovascular risk markers (such as diabetes or hyperlipidemia) is yet to be established. What can be said is that they should use information about heightened cardiovascular risk as further justification to pursue a healthy diet and lifestyle.

• 24.
  

  a) F b) F c) T d) F e) F

Increase in circulating hormones is one of the causes of skin changes during pregnancy. However, compression from the enlarging uterus, expansion of intravascular volume, and other less well-defined molecular and cellular phenomena are also responsible of such manifestations. Pruritus is present in only some skin disorders of pregnancy like polymorphous eruption of pregnancy, atopic eruption and pemphigoid gestationis. It is also a constant manifestation of intrahepatic cholestasis. Although skin changes become obvious mostly in the third trimester, all other periods of pregnancy and the immediately post-partum period can show skin problems. In most cases, skin changes are physiological and clinical diagnosis is sufficient to rule out more severe entities. Medical intervention is usually not required when skin manifestations are physiological.

• 25.
  

  a) F b) T c) T d) F e) F

Physiological skin changes are usually reversible within months after delivery. However, many skin changes can persist after that time like hyperpigmentation and striae distensae. Usually physiological skin changes are the result of hormonal and systemic adaptation of the body to pregnancy. They are benign and need no specific intervention. The areolas and the nipples are the most commonly affected sites when hyperpigmentation develops due to hormonal changes. The face, the periumbilical region and the folds are other common sites of hyperpigmentation. It is only when abnormally numerous spider telangiectasias manifest in pregnant women, that liver status should be checked, since in hepatic diseases estrogen catabolism may decrease. Treatment with pulsed dye laser or tretinoin cream of recent purplish striae may partially improve their appearance but should of course be given after delivery only. Retinoids are strictly contra indicated in pregnant and lactating women.

• 26.
  

  a) F b) T c) T d) F e) F

Involvement of peri-umbilical skin is suggestive of pemphigoid gestationis. Direct immunofluorescence or ELISA anti BPAg1 NC16 is necessary to confirm the diagnosis. Polymorphic eruption of pregnancy predominantly affects primigravidae in their third trimester. However earlier or postpartum onset is possible. Pruritus suggests intrahepatic cholestasis when there are no primary skin lesions. In one third of cases, excoriations secondary to scratching can be found. Serum bile salts levels should be tested whenever generalized pruritis develops with no primary skin lesions during pregnancy in order to rule out intrahepatic cholestasis.

• 27.
  

  a) T b) T c) F d) T e) T

Since direct immunofluorescence is negative, polymorphic eruption of pregnancy is the most probable diagnosis. Treatment will be only symptomatic. The main measure is the generous application of potent topical steroids. Emollients and Antihistamines can be used to add some effect. Some authors have reported that oral steroids are needed to relieve severe pruritus. However, topical potent or ultra-potent steroids are first line treatment in polymorphic eruption of pregnancy and systemic steroids should be avoided if possible. UVB phototherapy has an anti-inflammatory effect. It can help in some cases by reducing erythema severity and improving pruritis.

• 28.
  

  a) F b) F c) T d) F e) F

High maternal phenylalanine levels cross the placenta and lead to the maternal PKU syndrome. As the metabolic block is in the conversion of phenylalanine to tyrosine, maternal tyrosine levels will often be low and may require supplementation. Treatment aims to reduce maternal dietary sources of phenylalanine, an amino acid constituent of dietary protein, hence a low protein diet is advised. The risk of the maternal PKU syndrome is very high in women with phenylalanine levels ≥1200 umol/L: 92% of such babies will have mental retardation, 73% microcephaly, 12% congenital cardiac disease and 40% low birth weight. As the fetus develops, maternal protein tolerance increases and dietary protein intake needs to be increased in order to maintain metabolic control and facilitate fetal growth.

• 29.
  

  a) F b) T c) F d) F e) T

Although women have presented with metabolic decompensation in pregnancy – most cases of severe decompensation occur in the post-partum period and are thought to relate to the metabolic changes of the puerperium and the increased protein load for catabolism as the uterus involutes. The uterus weighs 900g at delivery, 450g at 1 week and by 3 months has returned to its normal weight of 55g. As in any condition associated with risk of cardiomyopathy, women with GSD III need to be assessed by a cardiologist in pregnancy. Many remain asymptomatic and have successful pregnancies but worsening of cardiac disease has been described. Elevated maternal phenylalanine levels can be detected in breast-milk. However, in an unaffected (heterozygote) baby, dietary milk protein (including phenylalanine) can readily be metabolized and breastfeeding can be encouraged. Early ovarian insufficiency, including primary amenorrhoea, is frequent among girls and women with galactosemia. To ensure adequate breast and uterine development and optimum bone health, assessment and monitoring should start around the age of 10–12 years. Pregnancy is a pro-thrombotic period and presentation of hypercoagulable conditions eg. homocystinuria during pregnancy and the postpartum period with a thrombus is well described. This risk of this can be reduced with good control of maternal homocysteine levels. There are no established specific guidelines but many metabolic physicians advise additional prophylaxis with LMWH during pregnancy and the post-partum period.

• 30.
  

  a) F b) F c) T d) F e) F

First trimester exposure to paroxetine is associated with a small increased risk of congenital cardiovascular malformations in some studies. Studies have not definitively reported increased risk of major congenital malformations with fluoxetine, sertraline, citalopram or escitalopram.